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آثار تمرین هم زمان(مقاومتی-استقامتی) بر بیان ژن های اینترفرون گاما، اینترلوکین 18 و فاکتور رشد تراریختی بتا در لکوسیت زنان سالم و دیابتی نوع 2 Effects of Concurrent Training (Resistance-Endurance) on Interferon-γ, Interloukin-18 and Transforming Growth Factor-β Gene Expression in Women with Type 2 Diabetes 1 1 مقدمه: تمرینات استقامتی موجب افزایش بیان ژن سایتوکاین های ضد التهابی و کاهش بیان ژن سایتوکین های پیش التــهابی در افراد ســالم می شوند با این وجود، تحقیقات در خصوص نقش تمرینات هم زمان بر بیان ژن این سایتوکین ها در افراد دیابتی محدود است. بنا بر این هدف از تحقیق حاضر تعیین آثار تمرین هم زمان بر بیان ژن سایتوکاین های پیش التهابی و ضد التهابی در لکوسیت زنان سالم و دیابتی نوع 2 بود. مواد و روش ها: در این مطالعه، 12 نفر از زنان دیابتی با محدوده سنی 38-30 سال به صورت تصادفی انتخاب و در سه گروه تمرین هم زمان(سالم 6 نفر) تمرین هم زمان(دیابتی 6 نفر) و کنترل دیابتی(6 نفر) قرار گرفتند. پروتکل تمرینی هم زمان شامل اجرای تمرین مقاومتی به روش درونگرا سه ست 8 تکراری با 80 درصـــد یک تکرار بیشینه( ) و سپس تمرین استقامتی دویدن بر روی تردمیل به مدت سی دقیقه(سه ست 10 دقیقه ای) با شدت 80-70 درصد حداکثر ضربان قلب بود. میزان بیان ژن mRNA (IFN-γ, IL-18 and TGF-β) لکوسیت های خون از طریق تکنیک Real time-PCR و بیان کمی ژن ها با استفاده از روش2-∆∆CT  محاسبه گردید. از آزمون آماری(permutation t-test) و آنوای یک راهه مستقل جهت تعیین تفاوت متغیرها ‎‏استفاده گردید. یافته های پژوهش: یافته های مطالعه حاضر نشان داد که کاهش میزان بیان ژن اینترفرون گاما و عامل رشد تراریختی بتا در زنان سالم و دیابتی نوع 2 بعد از فعالیت نسبت گروه کنترل معنادار نبود(P>0.05). علاوه بر این، نتایج تحقیق نشان داد که ژن اینترلوکین 18 در لکوسیت زنان سالم و دیابتی نوع 2 بلافاصله بعد از تمرین بیان نشده است(P>0.05).  بحث و نتیجه گیری: نتاج حاصل از پژوهش حاضر بیانگر آن است که تمرین هم زمان در یک وهله نمی ­تواند تغییر معناداری را در بیان ژن اینترفرون گاما، عامل رشد تراریختی بتا و اینترلوکین 18 ایجاد کند. برای ایجاد تغییرات احتمالاً به مدت و شدت بالاتری از این نوع تمرین نیاز باشد. 2 Introduction: High-intensity training increases the expression of anti-inflammatory cytokines and decreases the expression of pre-inflammatory cytokines in healthy individuals. However, there is limited research investigating the role of concurrent training in the expression of these cytokines in diabetics. This study aimed to evaluate the effect of concurrent training on the gene expression of pre-inflammatory and anti-inflammatory cytokines in females with type 2 diabetes.   Materials & Methods: In total, 12 diabetic patients (age range: 30-38 years) were selected randomly and divided into concurrent training (healthy cases, n=6), concurrent training (diabetic cases, n=6), and control (diabetic cases, n=6). The concurrent training protocol consisted of three isometric resistance training sessions with 3 sets of 8 with 80% of their one maximum repetition (  per week. Moreover, the endurance training included 30-min running (3 sets of 10 min) on a treadmill with a 70%-80% maximum heart rate. The amount of the mRNA gene expression in leukocyte (Interferon-γ[IFN-γ], Interloukin-18[IL-18], and Transforming Growth Factor [TGF-β]) was determined by the Real time-PCR technique. Quantitative gene expression was calculated using the 2-ΔΔ CT method. The differences in variables were determined by the independent t-test (permutation test) and one-way ANOVA. Ethics code: 1393.10.15   Findings: The healthy and diabetic cases showed no significant difference in terms of reduction in the IFN-γ and TGF-β mRNA gene expression after training, compared to the control group (P>0/05). In addition, the results showed that IL-18 mRNA gene was not expressed in leukocytes of healthy and diabetic cases immediately after training (P>0.05).   Discussions & Conclusions: In conclusion, the results suggest that concurrent training in one session is not able to create an alteration in the expression of IFN-γ, IL-18, and TGF-β. This type of exercise training may require a longer duration and greater intensity to make changes. 1 11 2020/05/19 1399/2/30 2020/09/16 1399/6/26 مریم حیدریان گروه فیزیولوژی ورزشی، دانشکده علوم ورزشی، دانشگاه رازی، کرمانشاه، ایران ایران امیرعباس منظمی Amirabbas monazzami گروه فیزیولوژی ورزشی، دانشکده علوم ورزشی، دانشگاه رازی، کرمانشاه، ایران ایران monazzami.amirabbas@gmail.com ناصر بهپور گروه فیزیولوژی ورزشی، دانشکده علوم ورزشی، دانشگاه رازی، کرمانشاه، ایران ایران علی مصطفایی مرکز تحقیقات بیولوژیک، دانشگاه علوم پزشکی کرمانشاه، کرمانشاه، ایران ایران Type 2 Diabetes Concurrent Training TGF-β IFN-γ IL-18 دیابت نوع 2 تمرینات هم زمان اینترفرون گاما عامل تغییر رشد بتا اینترلوکین 18 Gokhale R, Chandrashekara S, Vasanthakumar KC. Cytokine response to strenuous exercise in athletes and non athlete an adaptive response. Cytokine2007;40:123-7. doi: 10.1016/j.cyto.2007.08.006.##Medeiros NDS, Abreu FG, Colato AS, Lemos LS, Ramis TR, Dorneles GP, et al. Effects of concurrent training on oxidative stress and insulin resistance in obese individuals. Oxida Med Cell Longe2015; 697181. doi.10.1155/2015/697181.##Kuryłowicz A, Kozniewski K. Anti inflammatory strategies targeting metaflammation in type 2 diabetes . Molecules 2020; 25: 2224. doi.10.3390/molecules25092224.##Correa, Fernanda O B. The short-term effectiveness of non-surgical treatment in reducing levels of interleukin-1beta and proteases in gingival crevicular fluid from patients with type 2 diabetes mellitus and chronic periodontitis. J Periodontol 2008;11: 2143-50. doi: 10.1902/jop.2008.080132.##Carraro L, Ferraresso S, Cardazzo B, Romualdi C, Montesissa C, Gottardo F, et al. Expression profiling of skeletal muscle in young bulls treated with steroidal growth promoters. Physiol Genom2009; 38.138-48. doi.10.1152/physiol gen.00014.##Lee YH, Bae SC. Association between interferon-γ +874 T/A polymorphism and susceptibility to autoimmune diseases a meta-analysis. Lupus 2016; 25:710-718. doi. 10.1177/0961203315624557.##Cruz M, Maldonado C, Mondragon R, Sanchez R, Wacher NH, Carvajal G, et al. Glycine treatment decreases proinflammatory cytokines and increases interferon gamma in patients with type 2diabetes. J Endo Invest2008;31:.694-9. doi.10.1007/BF03346417.##mcgillicuddy FC, Chiquoine EH, Hinkle CC, Kim RJ, Shah R, Roche HM, et al. Interferon gamma attenuates insulin signaling, lipid storage and differentiation in human adipocytes via activation of the JAK/STAT pathway. J Biol Chem 2009;284:31936-44. doi.10.1074/jbc. M109.061655##Katarzyna S, Rafal M, Anna ZM, Anna PK, Piotr S, Natalia WK, et al. Interleukin6 and Interleukin15 as possible biomarkers of the risk of autoimmune diabetes development. Biomed Res Int2019; 4734063. doi.10.1016/j. biopsycho. 2014.03.009##Leick L, Lindegaard B, Stensvold D, Plomgaard P, Saltin B, Pilegaard H. Adipose tissue interleukin18 mRNA and plasma interleukin18 effect of obesity and exercise. Obesit Silve Spring 2007;15:356-63. doi.10.1038/oby.2007.528##Colato A, Abreu F, Medeiros N, Lemos L, Dorneles G, Ramis T, et al. Effects of concurrent training on inflammatory markers and expression of CD4 and CD8 and HLA-DR in overweight and obese adults. J Exe Sci Fit2014; 12:55-61. doi.10.1016/j.jesf.2014.06.002##Bastard JP, Maachi M, Lagathu C, Kim MJ, Caron M, Vidal H, et al. Recent advances in the relationship between obesity inflammation, and insulin resistance. European Cyt Net2006; 17:4-12.##Saremi A. [Comparison of the effects of endurance resistance and concurrent training on insulin resistance and adiponectin-leptin ratio in diabetic Rat]. J QUMS2017; 21:13-22. (Persian)##Emma LL, Andrew HB, Angela CB. TGFβ smooth muscle cells and coronary artery disease a review. Cel Sig 2019; 53: 90-101. doi.10.1016/j.cellsig.2018.09.004##Zanuso S, Jimenez A, Pugliese G, Corigliano G, Balducci S. Exercise for the management of type 2 diabetes a review of the evidence. Acta Diabetol 2010;47:15-22. doi. 0.1007/s00592-009-0126-3##Thomas W, Buford MBC, Brian D, Shelmadine M. Effects of eccentric treadmill exercise on inflammatory gene expression in human skeletal muscle. Appl Physiol Nutr Met. 2009;34:745-53. doi.org/10.1139/H09-067.##Cheyne E, Donges RD, Greg C, Michael J. Cytokine mRNA expression responses to resistance aerobic and concurrent exercise in sedentary middle aged men. Appli Physiol Nut Metab2014;39:130-7. doi.10. 1139/apnm-2013076##Monazzamiamirabbas RH, Ghrakhanlou R, Yari Kh, Rahimi Z. Modulation of oxidative and glycolytic skeletal muscle fibers Na+/H+ exchanger1 and Na+/HCO3- co-transporter genes and proteins expression in type2 diabetic Rat streptozotocin + high fat diet following long term endurance training. CMB2017;63:8-11. doi.10.14715/cmb/2017.63.5.3##Libardi CA, Souza GV, Cavaglieri CR, Madruga VA, et al. Effect of resistance endurance and concurrent training on TNF-α, IL-6 and CRP. Med Sci Spor Exe 2012; 44; 51-6. doi. 10.1249/MSS.0b013e318229d2e9##Atashak S, Stannard SR, Azizbeigi k. Cardiovascular risk factors adaptation to concurrent training in overweight sedentary middle aged men. J Sport Med Phys Fit2016; 56:624-30##Yamamoto SN, Umeda T, Matsuzaka M, Takahashi I, Tanabe M, Danjo K, Kojima A, et al. Effects of long term training on neutrophil function in male university judoists. British J Sport Med2008;42:255-9. doi.10.1074/jbc.RA119.009596##Tammela T, Enholm B, Alitalo K, Paavonen K. The biology of vascular endothelial growth factors. Cardio Res2005;65:550-63. doi.10.1016/j.cardiores.2004.12.002##Atashak S. [The effect of the eight-week progressive concurrent training on inflammatory index of cardiovascular disease predictor, and body composition in sedentary middle age Men]. Iranian J Cardiovas Nurs2013; 2:16-25. (Persian)##Eskandary S, Rahimi E. [Effects of eight weeks aerobic training, resistance training and concurrent training on the metabolic syndrome and HbA1c in men with type 2 diabetes]. J Phys Act Horm2017; 1; 51-64. (Persian).##Aikens JE, Perkins DW, Piette JD, Lipton B. Association between depression and concurrent Type 2 diabetes outcomes varies by diabetes regimen. Diabet Med2008; 25:1324-9. doi. 10.1111/j.1464-5491##Abdi A, Mehrabani J, Nordvall M, Wong A, Fallah A, Bagheri R. Effects of concurrent training on irisin and fibronectin type III domain containing 5 expression in visceral adipose tissue in type-2 diabetic rats. Arch Physiol Biochem2020;1-6. doi.10.1080/13813455.2020.1716018##Ogorman DJ, Karlsson HK, Mcquaid S, Yousif O, Rahman Y, Gasparro D, et al. Exercise training increases insulin stimulated glucose disposal and GLUT4 protein content in patients with type 2 diabetes. Diabetologia 2006;49:2983-92. doi.10.1007/s00125-006-457-3##Balducci S, Zanuso S, Nicolucci A, Fernando F, Cavallo S, Cardelli P, et al. Anti inflammatory effect of exercise training in subjects with type 2 diabetes and the metabolic syndrome is dependent on exercise modalities and independent of weight loss. Nut Metab Cardiovas Dis2010;20:608-17. doi.10.1016/j.numecd.2009.04.015##Bruun JM, Stallknecht B, Helge JW, Richelsen B. Interleukin18 in plasma and adipose tissue effects of obesity, insulin resistance and weight loss. European J Endocrinol2007;157:465-71. doi.10.1530/ EJE-07-0206.##Gokhale R, Chandrashekara S, Vasanthakumar KC. Cytokine response to strenuous exercise in athletes and non athlete an adaptive response. Cytokine2007;40:123-7. doi: 10.1016/j.cyto.2007.08.006.##Medeiros NDS, Abreu FG, Colato AS, Lemos LS, Ramis TR, Dorneles GP, et al. Effects of concurrent training on oxidative stress and insulin resistance in obese individuals. Oxida Med Cell Longe2015; 697181. doi.10.1155/2015/697181.##Kuryłowicz A, Kozniewski K. Anti inflammatory strategies targeting metaflammation in type 2 diabetes . Molecules 2020; 25: 2224. doi.10.3390/molecules25092224.##Correa, Fernanda O B. The short-term effectiveness of non-surgical treatment in reducing levels of interleukin-1beta and proteases in gingival crevicular fluid from patients with type 2 diabetes mellitus and chronic periodontitis. J Periodontol 2008;11: 2143-50. doi: 10.1902/jop.2008.080132.##Carraro L, Ferraresso S, Cardazzo B, Romualdi C, Montesissa C, Gottardo F, et al. Expression profiling of skeletal muscle in young bulls treated with steroidal growth promoters. Physiol Genom2009; 38.138-48. doi.10.1152/physiol gen.00014.##Lee YH, Bae SC. Association between interferon-γ +874 T/A polymorphism and susceptibility to autoimmune diseases a meta-analysis. Lupus 2016; 25:710-718. doi. 10.1177/0961203315624557.##Cruz M, Maldonado C, Mondragon R, Sanchez R, Wacher NH, Carvajal G, et al. Glycine treatment decreases proinflammatory cytokines and increases interferon gamma in patients with type 2diabetes. J Endo Invest2008;31:.694-9. doi.10.1007/BF03346417.##mcgillicuddy FC, Chiquoine EH, Hinkle CC, Kim RJ, Shah R, Roche HM, et al. Interferon gamma attenuates insulin signaling, lipid storage and differentiation in human adipocytes via activation of the JAK/STAT pathway. J Biol Chem 2009;284:31936-44. doi.10.1074/jbc. M109.061655##Katarzyna S, Rafal M, Anna ZM, Anna PK, Piotr S, Natalia WK, et al. Interleukin6 and Interleukin15 as possible biomarkers of the risk of autoimmune diabetes development. Biomed Res Int2019; 4734063. doi.10.1016/j. biopsycho. 2014.03.009##Leick L, Lindegaard B, Stensvold D, Plomgaard P, Saltin B, Pilegaard H. Adipose tissue interleukin18 mRNA and plasma interleukin18 effect of obesity and exercise. Obesit Silve Spring 2007;15:356-63. doi.10.1038/oby.2007.528##Colato A, Abreu F, Medeiros N, Lemos L, Dorneles G, Ramis T, et al. Effects of concurrent training on inflammatory markers and expression of CD4 and CD8 and HLA-DR in overweight and obese adults. J Exe Sci Fit2014; 12:55-61. doi.10.1016/j.jesf.2014.06.002##Bastard JP, Maachi M, Lagathu C, Kim MJ, Caron M, Vidal H, et al. Recent advances in the relationship between obesity inflammation, and insulin resistance. European Cyt Net2006; 17:4-12.##Saremi A. [Comparison of the effects of endurance resistance and concurrent training on insulin resistance and adiponectin-leptin ratio in diabetic Rat]. J QUMS2017; 21:13-22. (Persian)##Emma LL, Andrew HB, Angela CB. TGFβ smooth muscle cells and coronary artery disease a review. Cel Sig 2019; 53: 90-101. doi.10.1016/j.cellsig.2018.09.004##Zanuso S, Jimenez A, Pugliese G, Corigliano G, Balducci S. Exercise for the management of type 2 diabetes a review of the evidence. Acta Diabetol 2010;47:15-22. doi. 0.1007/s00592-009-0126-3##Thomas W, Buford MBC, Brian D, Shelmadine M. Effects of eccentric treadmill exercise on inflammatory gene expression in human skeletal muscle. Appl Physiol Nutr Met. 2009;34:745-53. doi.org/10.1139/H09-067.##Cheyne E, Donges RD, Greg C, Michael J. Cytokine mRNA expression responses to resistance aerobic and concurrent exercise in sedentary middle aged men. Appli Physiol Nut Metab2014;39:130-7. doi.10. 1139/apnm-2013076##Monazzamiamirabbas RH, Ghrakhanlou R, Yari Kh, Rahimi Z. Modulation of oxidative and glycolytic skeletal muscle fibers Na+/H+ exchanger1 and Na+/HCO3- co-transporter genes and proteins expression in type2 diabetic Rat streptozotocin + high fat diet following long term endurance training. CMB2017;63:8-11. doi.10.14715/cmb/2017.63.5.3##Libardi CA, Souza GV, Cavaglieri CR, Madruga VA, et al. Effect of resistance endurance and concurrent training on TNF-α, IL-6 and CRP. Med Sci Spor Exe 2012; 44; 51-6. doi. 10.1249/MSS.0b013e318229d2e9##Atashak S, Stannard SR, Azizbeigi k. Cardiovascular risk factors adaptation to concurrent training in overweight sedentary middle aged men. J Sport Med Phys Fit2016; 56:624-30##Yamamoto SN, Umeda T, Matsuzaka M, Takahashi I, Tanabe M, Danjo K, Kojima A, et al. Effects of long term training on neutrophil function in male university judoists. British J Sport Med2008;42:255-9. doi.10.1074/jbc.RA119.009596##Tammela T, Enholm B, Alitalo K, Paavonen K. The biology of vascular endothelial growth factors. Cardio Res2005;65:550-63. doi.10.1016/j.cardiores.2004.12.002##Atashak S. [The effect of the eight-week progressive concurrent training on inflammatory index of cardiovascular disease predictor, and body composition in sedentary middle age Men]. Iranian J Cardiovas Nurs2013; 2:16-25. (Persian)##Eskandary S, Rahimi E. [Effects of eight weeks aerobic training, resistance training and concurrent training on the metabolic syndrome and HbA1c in men with type 2 diabetes]. J Phys Act Horm2017; 1; 51-64. (Persian).##Aikens JE, Perkins DW, Piette JD, Lipton B. Association between depression and concurrent Type 2 diabetes outcomes varies by diabetes regimen. Diabet Med2008; 25:1324-9. doi. 10.1111/j.1464-5491##Abdi A, Mehrabani J, Nordvall M, Wong A, Fallah A, Bagheri R. Effects of concurrent training on irisin and fibronectin type III domain containing 5 expression in visceral adipose tissue in type-2 diabetic rats. Arch Physiol Biochem2020;1-6. doi.10.1080/13813455.2020.1716018##Ogorman DJ, Karlsson HK, Mcquaid S, Yousif O, Rahman Y, Gasparro D, et al. Exercise training increases insulin stimulated glucose disposal and GLUT4 protein content in patients with type 2 diabetes. Diabetologia 2006;49:2983-92. doi.10.1007/s00125-006-457-3##Balducci S, Zanuso S, Nicolucci A, Fernando F, Cavallo S, Cardelli P, et al. Anti inflammatory effect of exercise training in subjects with type 2 diabetes and the metabolic syndrome is dependent on exercise modalities and independent of weight loss. Nut Metab Cardiovas Dis2010;20:608-17. doi.10.1016/j.numecd.2009.04.015##Bruun JM, Stallknecht B, Helge JW, Richelsen B. Interleukin18 in plasma and adipose tissue effects of obesity, insulin resistance and weight loss. European J Endocrinol2007;157:465-71. doi.10.1530/ EJE-07-0206.## ##

L-گلوتامین با کاهش سیتوکین های پیش التهابی، اکسید نیتریک و بیان CD40، اندوتوکسمی را مهار می کند L-Glutamin-Induced Inhibition of Endotoxemia by Reducing Pre-Inflammatory Cytokines, Nitric Oxide, and CD40 Expression 1 1 مقدمه: پژوهشگران در سال های اخیر در حال بررسی پاتوژنز اصلی درگیر در شوک سپتیک ناشی از لیپوپلی ساکارید بوده اند و استفاده از داروهای مناسب در جهت مداخله با پاتوزنز، دغدغه اصلی آن ها بوده است. بنا بر ابن هدف از این مطالعه، بررسی اثر ال گلوتامین به عنوان القاء کننده HSP 70 در کاهش سیتوکاین های پیش التهابی و واسطه های موثر در شوک سپتیک از جمله تولید نیتریک اکساید و بیان CD 40 در موش های تحت تجویز با LPS می باشد. مواد و روش ها: 25 سر موش نر نژاد swiss albino به طور تصادفی به 3 گروه تقسیم شدند ، شامل گروه A (n=5) یا گروه کنترل، گروه B (n=10) دریافت کننده LPS با دوز 75/0 میلی گرم به ازای هر حیوان به صورت داخل صفاقی و گروه C (n=10) دریافت کننده ال گلوتامین با دوز 50 میلی گرم به ازای هر کیلوگرم وزن حیوان(3 دز هر 24 ساعت 30 دقیقه بعد تزریق  LPS) به صورت داخل صفاقی  می باشد. سپس یک روز بعد از تجویز دارو به بررسی سایتوکاین های TNF-α،IFN-γ ،IL-4 ، IL-10، HSP70، CD40 و نیتریک اکساید پرداخته شد. یافته های پژوهش: تجزیه و تحلیل داده ها با روش آنالیز واریانس یک طرفه Scheffe test توسط نرم افزارSPSS vol.19  نشان داد ال گلوتامین می تواند باعث کاهش معنی دار سطح سرمی سایتوکاین پیش التهابی، نیتریک اکساید و بیان CD 40 در گروه تحت درمان با دارو(گروه C) نسبت به گروه تحت تجویز LPS (گروه B) شود(P<0.05). بحث و نتیجه گیری: ال گلوتامین به واسطه کاهش سطح واسطه های التهابی می تواند گزینه ای مناسب برای درمان باشد.   2 Introduction: Researchers have been investigating the major pathogens involved in septic shock caused by lipopolysaccharide in recent years. Moreover, they have been concerned about the use of appropriate drugs to intervene with the main pathogenesis of the disease. This study aimed to investigate the effect of L-Glutamine as an HSP70 inducer in reducing pre-inflammatory cytokines and effective intermediaries in septic shock, including nitric oxide production and CD40 expression in mice treated with lipopolysaccharide (LPS).   Materials & Methods: In total, 25 Swiss Albino mice were randomly divided into three groups of A (control group, n=5), (received LPS with a dose of 0.75 mg/animal intraperitoneally [IP], (n=10), and (received L-glutamine with a dose of 50 mg/kg IP 30 minutes after the injection of LPS [three doses every 24 h], (n=10). Subsequently, one day after the final dose of drug induction, the number of cytokines, such as IFN-γ, IL-4, IL-10, HSP70, CD40, and nitric oxide, were evaluated in this study. Ethics code: IR.TABRIZU.REC.1398.003   Findings: The data were analyzed in SPSS software (version 19) through a one-way analysis of variance and Scheffe test. According to the results, L-glutamine can significantly reduce the serum levels of pre-inflammatory cytokine, nitric oxide, and CD40 expression in the drug-treated group (group C), compared to the LPS- treated group (group B) (P<0.05).   Discussions & Conclusions: L-glutamine could be a good choice for treatment by reducing the level of inflammatory mediators. 12 24 2020/05/192019/12/18 1398/9/27 2020/09/162020/05/26 1399/3/6 یاسر جعفری خطایو Yaser Jafari khataylou گروه پاتوبیولوژی، دانشکده دام پزشکی، دانشگاه تبریز، تبریز، ایران ایران y.jafari@tabrizu.ac.ir سمیه احمدی افشار Somayeh Ahmadiafshar گروه میکروبیولوژی، دانشکده دام پزشکی دانشگاه ارومیه، ارومیه، ایران ایران afsharnegin92@gmail.com Heat shock protein70 L-glutamine Lipopolysaccharide Nitric oxide پروتئین شوک حرارتی ال گلوتامین لیپو پلی ساکارید نیتریک اکساید Kobayashi M, Tsuda Y, Yoshida T, Takeuchi D, Utsunomiya T, Takahashi H, et al. Bacterial sepsis and chemokines. Curr Drug Targ 2006; 7: 119-34. doi. 10.2174/138945006775270169##Marino LV, Pathan N, Meyer R, Wright V, Habibi P. Glutamine depletion and heat shock protein 70 in children with meningococcal disease. Clin Nutr 2014; 33:915-21. doi.10.1016/j.clnu.2013.09.013##Wang Y, Kelly CG, Karttunen JT, Whittall T, Lehner PJ, Duncan L, et al. CD40 is a cellular receptor mediating mycobacterial heat shock protein 70 stimulation of CC-chemokines. Immunity 2001; 15:971-83. doi.10.1016/S1074-7613(01)00242-4##Ramana KV, Fadl AA, Tammali R, Reddy AB, Chopra AK, Srivastava SK. Aldose reductase mediates the lipopolysaccharide induced release of inflammatory mediators in RAW264.7 murine macrophages. J Biol Chem 2006 Nov 3;281:33019-29. doi. 10.1074/jbc.M603819200.##Newsholme EA, Parry M. Properties of glutamine release from muscle and its importance for the immune system J Par Ent Nutr1990;14:63-7. doi. 10.1177/014860719001400406.##Ko HM, Oh SH, Bang HS, Kang NI, Cho BH, Im SY, et al. Glutamine protects mice from lethal endotoxic shock via a rapid induction of MAPK phosphatase-1. J Immunol 2009; 182:7957-62. doi.10.4049/jimmunol.0900043.##Carrillo A, Lardone PJ, Naji L, Fernandez JM, Martin I, Guerrero JM, et al. Beneficial pleiotropic actions of melatonin in an experimental model of septic shock in Mice regulation of pro-/anti-inflammatory cytokine network, protection against oxidative damage and anti-apoptotic effects. J Pineal Res 2005; 39: 400-408. doi.10.1111/j.1600-079X.2005.00265. x.##Jafarikhatailou Y, Delirezh N, Farshid AA, Zafarshamspoor S, Shahabi SH. Effect of L-Glutamine on fasting blood sugar and pathological lesions of autoimmune diabetes in male C57BL/6 mice. Stud Med Sci 2012; 23:133-40.##Mishra KP, Rani R, Yadav VS, Naik S. Effect of lead exposure on lymphocyte subsets and activation markers. Immunopharmacol Immunotoxicol 2010; 32:446-9. doi.10.3109/08923970903503668.##Azadmehr A, Afshari A, Baradaran B, Hajiaghaee R, Rezazadeh SH, Monsefesfahani H. Suppression of nitric oxide production in activated murine peritoneal macrophages in vitro and ex vivo by scrophularia striata ethanolic extract. Ethnopharmacol 2009; 124:166-169. doi.10.1016/j.jep.2009.03.042##Guzik TJ, Korbut R, Adamek T. Nitric oxide and superoxide in inflammation and immune regulation. J Physiol Pharmacol, :469-87.##Lindros KO, Jarvelainen HA. Chronic systemic endotoxin exposure an animal model in experimental hepatic encephalopathy. Metab Brain Dis2005; 20: 393-8. doi.10.1007/s11011-005-7924-2.##Oliveira GP, Dias CM, Pelosi P, Rocco PR. Understanding the mechanisms of glutamine action in critically ill patients. An Acad Bras Cienc 2010; 82:417-30. doi.10.1590/s0001-37652010000200018.##Lecleire S, Hassan A, Marion R, Antonietti M, Savoye G, Bole C, et al. Combined glutamine and arginine decrease proinflammatory cytokine production by biopsies from Crohns patients in association with changes in nuclear factor kappaB and p38 mitogen activated protein kinase pathways. J Nutr 2008; 138:2481-6. doi. 10.3945/jn.108.099127.##Cruzat V, Macedo M, Noel K, Curi R, Newsholme P. Glutamine metabolism and immune function, supplementation and clinical translation. Nutrients 2018; 23:10. doi.10.3390/nu10111564.##Jacque N, Ronchetti AM, Larrue C, Meunier G, Birsen R, Willems L, et al. Targeting glutaminolysis has antileukemic activity in acute myeloid leukemia and synergizes with BCL-2 inhibition. Blood 2015; 126:1346-56. doi.10.1182/blood-2015-01-621870.##Xuefeng W, Lei H, Yanxia Qu, Hongmei Lv, Xiaohua He. Effects of glutamine on cytokines 1L-1 and TNF-α in rehabilitation and prognosis of patients with lobectomy. Exp Ther Med. 2018; 16: 2303-08. doi.10.3892/etm.2018.6443##Ferat E, Sanchez A, Gutierrez M, Bosco I, Wong I, Pastelin R, et al. Heat shock protein 70 down regulates the production of toll like receptor induced pro inflammatory cytokines by a heat shock factor-1/constitutive heat shock element binding factor dependent mechanism. J Inflamm 2014; 12; 11:19. doi.10.1186/1476-9255-11-19.##Barquera C, Rivera RRy. Obesidad en Mexico epidemiologia y politicas de salud para su control y prevencion. Gac Med Mex 2010; 146:397-407.##Luo X, Zuo X, Mo X, Zhou Y, Xiao X. Treatment with recombinant Hsp72 suppresses collagen induced arthritis in Mice. Inflammation 2011; 34:432-9.##Bangen JM, Schade FU, Flohe SB. Diverse regulatory activity of human heat shock proteins 60 and 70 on endotoxin induced inflammation. Biochem Biophys Res Commun2007; 359:709-15. doi.10.1016/j.bbrc.2007.05.167.##Becker T, Hartl FU, Wieland F. CD40 an extracellular receptor for binding and uptake of Hsp70 peptide complexes. J Cell Biol 2002; 30; 158:1277-85. dol: 10.1083/ jcb.200208083.##Zitvogel L, Kepp O, Kroemer G. Decoding cell death signals in inflammation and immunity. Cell 2010; 109: 4839-45. doi.10.1016/j.cell.2010.02.015##Dalpke A, Zimmermann S, Heeg K. CpG DNA in the Prevention and treatment of infections. Biodrugs 2002; 16: 419-31. doi.10.2165/00063030-200216060-00003.##Bryk J, Ochoa JB, Correia MI, Munera V, Popovic PJ. Effect of citrulline and glutamine on nitric oxide production in RAW 264.7 cells in an arginine depleted environment. J Parent Ent Nutr 2008; 32:377-83. doi.10.1177/0148607108319807.##Zanin A, Nussbaum G, Franitza S, Cohen IR, Lider O. T cells respond to heat shock protein 70 via TLR4 activation of adhesion and inhibition of chemokine receptors. Faseb J 2003; 17:1567-9. doi.10.1096/fj.02-1139fje##Hayashi Y, Sawa Y, Fukuyama N, Nakazawa H, Matsuda H. Preoperative glutamine administration induces heat shock protein 70 expression and attenuates cardiopulmonary bypass induced inflammatory response by regulating nitric oxide synthase activity. Circulation 2002; 106:2601-7. doi. 10.1161/01.cir.0000035651.72240.07.##Tone M, Tone Y, Babik JM, Lin CY, Waldmann H. The role of sp1 and NF-κB in regulating CD40 gene expression. J Biol Chem2002; 277:8890-7. doi.10.1074/ jbc.m109889200##Jong YP, Comiskey M, Kalled SL, Mizoguchi E, Flavell RA, Bhan AK, et al. Chronic murine colitis is dependent on the CD154/CD40 pathway and can be attenuated by anti-CD154 administration. Gastroenterology 2000; 119:715-23. doi.10.1053/gast.2000.16485##Pullen SS, Dang TT, Crute JJ, Kehry MR. CD40 signaling through tumor necrosis factor receptor-associated factors. Binding site specificity and activation of downstream pathways by distinct TRAFs. J Biol Chem 1999; 274:14246-54. doi. 10.1074/jbc.274.20.14246.## ##Kobayashi M, Tsuda Y, Yoshida T, Takeuchi D, Utsunomiya T, Takahashi H, et al. Bacterial sepsis and chemokines. Curr Drug Targ 2006; 7: 119-34. doi. 10.2174/138945006775270169##Marino LV, Pathan N, Meyer R, Wright V, Habibi P. Glutamine depletion and heat shock protein 70 in children with meningococcal disease. Clin Nutr 2014; 33:915-21. doi.10.1016/j.clnu.2013.09.013##Wang Y, Kelly CG, Karttunen JT, Whittall T, Lehner PJ, Duncan L, et al. CD40 is a cellular receptor mediating mycobacterial heat shock protein 70 stimulation of CC-chemokines. Immunity 2001; 15:971-83. doi.10.1016/S1074-7613(01)00242-4##Ramana KV, Fadl AA, Tammali R, Reddy AB, Chopra AK, Srivastava SK. Aldose reductase mediates the lipopolysaccharide induced release of inflammatory mediators in RAW264.7 murine macrophages. J Biol Chem 2006 Nov 3;281:33019-29. doi. 10.1074/jbc.M603819200.##Newsholme EA, Parry M. Properties of glutamine release from muscle and its importance for the immune system J Par Ent Nutr1990;14:63-7. doi. 10.1177/014860719001400406.##Ko HM, Oh SH, Bang HS, Kang NI, Cho BH, Im SY, et al. Glutamine protects mice from lethal endotoxic shock via a rapid induction of MAPK phosphatase-1. J Immunol 2009; 182:7957-62. doi.10.4049/jimmunol.0900043.##Carrillo A, Lardone PJ, Naji L, Fernandez JM, Martin I, Guerrero JM, et al. Beneficial pleiotropic actions of melatonin in an experimental model of septic shock in Mice regulation of pro-/anti-inflammatory cytokine network, protection against oxidative damage and anti-apoptotic effects. J Pineal Res 2005; 39: 400-408. doi.10.1111/j.1600-079X.2005.00265. x.##Jafarikhatailou Y, Delirezh N, Farshid AA, Zafarshamspoor S, Shahabi SH. Effect of L-Glutamine on fasting blood sugar and pathological lesions of autoimmune diabetes in male C57BL/6 mice. Stud Med Sci 2012; 23:133-40.##Mishra KP, Rani R, Yadav VS, Naik S. Effect of lead exposure on lymphocyte subsets and activation markers. Immunopharmacol Immunotoxicol 2010; 32:446-9. doi.10.3109/08923970903503668.##Azadmehr A, Afshari A, Baradaran B, Hajiaghaee R, Rezazadeh SH, Monsefesfahani H. Suppression of nitric oxide production in activated murine peritoneal macrophages in vitro and ex vivo by scrophularia striata ethanolic extract. Ethnopharmacol 2009; 124:166-169. doi.10.1016/j.jep.2009.03.042##Guzik TJ, Korbut R, Adamek T. Nitric oxide and superoxide in inflammation and immune regulation. J Physiol Pharmacol, :469-87.##Lindros KO, Jarvelainen HA. Chronic systemic endotoxin exposure an animal model in experimental hepatic encephalopathy. Metab Brain Dis2005; 20: 393-8. doi.10.1007/s11011-005-7924-2.##Oliveira GP, Dias CM, Pelosi P, Rocco PR. Understanding the mechanisms of glutamine action in critically ill patients. An Acad Bras Cienc 2010; 82:417-30. doi.10.1590/s0001-37652010000200018.##Lecleire S, Hassan A, Marion R, Antonietti M, Savoye G, Bole C, et al. Combined glutamine and arginine decrease proinflammatory cytokine production by biopsies from Crohns patients in association with changes in nuclear factor kappaB and p38 mitogen activated protein kinase pathways. J Nutr 2008; 138:2481-6. doi. 10.3945/jn.108.099127.##Cruzat V, Macedo M, Noel K, Curi R, Newsholme P. Glutamine metabolism and immune function, supplementation and clinical translation. Nutrients 2018; 23:10. doi.10.3390/nu10111564.##Jacque N, Ronchetti AM, Larrue C, Meunier G, Birsen R, Willems L, et al. Targeting glutaminolysis has antileukemic activity in acute myeloid leukemia and synergizes with BCL-2 inhibition. Blood 2015; 126:1346-56. doi.10.1182/blood-2015-01-621870.##Xuefeng W, Lei H, Yanxia Qu, Hongmei Lv, Xiaohua He. Effects of glutamine on cytokines 1L-1 and TNF-α in rehabilitation and prognosis of patients with lobectomy. Exp Ther Med. 2018; 16: 2303-08. doi.10.3892/etm.2018.6443##Ferat E, Sanchez A, Gutierrez M, Bosco I, Wong I, Pastelin R, et al. Heat shock protein 70 down regulates the production of toll like receptor induced pro inflammatory cytokines by a heat shock factor-1/constitutive heat shock element binding factor dependent mechanism. J Inflamm 2014; 12; 11:19. doi.10.1186/1476-9255-11-19.##Barquera C, Rivera RRy. Obesidad en Mexico epidemiologia y politicas de salud para su control y prevencion. Gac Med Mex 2010; 146:397-407.##Luo X, Zuo X, Mo X, Zhou Y, Xiao X. Treatment with recombinant Hsp72 suppresses collagen induced arthritis in Mice. Inflammation 2011; 34:432-9.##Bangen JM, Schade FU, Flohe SB. Diverse regulatory activity of human heat shock proteins 60 and 70 on endotoxin induced inflammation. Biochem Biophys Res Commun2007; 359:709-15. doi.10.1016/j.bbrc.2007.05.167.##Becker T, Hartl FU, Wieland F. CD40 an extracellular receptor for binding and uptake of Hsp70 peptide complexes. J Cell Biol 2002; 30; 158:1277-85. dol: 10.1083/ jcb.200208083.##Zitvogel L, Kepp O, Kroemer G. Decoding cell death signals in inflammation and immunity. Cell 2010; 109: 4839-45. doi.10.1016/j.cell.2010.02.015##Dalpke A, Zimmermann S, Heeg K. CpG DNA in the Prevention and treatment of infections. Biodrugs 2002; 16: 419-31. doi.10.2165/00063030-200216060-00003.##Bryk J, Ochoa JB, Correia MI, Munera V, Popovic PJ. Effect of citrulline and glutamine on nitric oxide production in RAW 264.7 cells in an arginine depleted environment. J Parent Ent Nutr 2008; 32:377-83. doi.10.1177/0148607108319807.##Zanin A, Nussbaum G, Franitza S, Cohen IR, Lider O. T cells respond to heat shock protein 70 via TLR4 activation of adhesion and inhibition of chemokine receptors. Faseb J 2003; 17:1567-9. doi.10.1096/fj.02-1139fje##Hayashi Y, Sawa Y, Fukuyama N, Nakazawa H, Matsuda H. Preoperative glutamine administration induces heat shock protein 70 expression and attenuates cardiopulmonary bypass induced inflammatory response by regulating nitric oxide synthase activity. Circulation 2002; 106:2601-7. doi. 10.1161/01.cir.0000035651.72240.07.##Tone M, Tone Y, Babik JM, Lin CY, Waldmann H. The role of sp1 and NF-κB in regulating CD40 gene expression. J Biol Chem2002; 277:8890-7. doi.10.1074/ jbc.m109889200##Jong YP, Comiskey M, Kalled SL, Mizoguchi E, Flavell RA, Bhan AK, et al. Chronic murine colitis is dependent on the CD154/CD40 pathway and can be attenuated by anti-CD154 administration. Gastroenterology 2000; 119:715-23. doi.10.1053/gast.2000.16485##Pullen SS, Dang TT, Crute JJ, Kehry MR. CD40 signaling through tumor necrosis factor receptor-associated factors. Binding site specificity and activation of downstream pathways by distinct TRAFs. J Biol Chem 1999; 274:14246-54. doi. 10.1074/jbc.274.20.14246.## ## ##

بررسی تاثیر کشت هم جوار باکتری لاکتوباسیلوس رامنوز بر میزان بیان ژن های casp3و bax در سلول های سرطانی کولون HT29 The Study of Expression of Casp3/Bax Genes in HT29 Colon Cancer Cell Line with Lactobacillus rhamnosus Co-Culturing 1 1 مقدمه: سرطان کولون در کشورهای توسعه یافته شیوع یافته است. باکتری های پروبیوتیک، نقش مهمی در کاهش ابتلا به سرطان کولون و درمان سرطان کولون را می توانند ایفا کنند هدف از این مطالعه بررسی تاثیر کشت هم جوار باکتری لاکتوباسیلوس رامنوز بر میزان بیان ژن های casp3 و bax در سلول های سرطانی است. مواد و روش ها: در این مطالعه تجربی آزمایشگاهی پس از کشت باکتری ها، مایع رویی و عصاره باکتریایی تهیه شده و سلول ها توسط این مواد تیمار شدند. اثرات سمیت سلولی عصاره سلول باکتری روی رده سلولی  HT29با استفاده از روشMTT  بررسی شد. پس از استخراج  RNAو تهیهcDNA ، میزان بیان ژن های bax،  casp3در رده سلولی  HT29با استفاده از روش Real Time PCR مورد بررسی قرار گرفت. یافته های پژوهش: نتایج آزمایشMTT  نشان داد که لاکتوباسیلوس رامنوز در غلظت 10 میکروگرم بر میلی لیتر باعث کاهش بقای سلول HT-29 به میزان 32/8±49/51 درصد شد و نتایج رنگ آمیزی دپی نشان داد تیمار سلول های  HT29با باکتری لاکتوباسیلوس رامنوز باعث تغییرات کیفی آپــــوپتوز سلـــولی می شود. نتایج Real time PCR نشان داد که باکتری های لاکتوباسیلوس رامنوز سبب افزایش معنی دار بیان ژن های bax (22/0±2/4) و casp3(12/0±88/6 (در مقایسه با ژن کنترل در سلول های سرطانی کولون HT29 شد(P<0.05).  بحث و نتیجه گیری: نتایج این مطالعه نشان داد که باکتری‌ های لاکتوباسیلوس رامنوز میزان بیان ژن ‌bax, cas3 را افزایش داده و سبب القای آپوپتوز در رده سلولی  HT29می شود. بنا بر این با انجام مطالعه های بیشتر می توان از این باکتری به عنوان یک محصول پروبیوتیک ضد سرطان در درمان و پیشگیری از سرطان کولون استفاده نمود. 2 Introduction: Colon cancer has spread to developed countries. Probiotic bacteria can play an important role in reducing cancer and treating colon cancer. The aim of this study was to determine the effect of adjacent bovine Lactobacillus rhamnose culture on the expression of casp3 and bax genes in cancer cell.   Materials & Methods: In this experimental study after bacterial culture, supernatant and bacterial extract were prepared and the cells were treated with these materials. The effects of cell cytotoxicity of the cell line on the HT29 cell line were investigated using MTT method. After extraction of RNA and preparation of cDNA, the expression of bax, casp3 genes in the HT29 cell line was investigated using Real Time PCR.   Findings: The results of MTT assay showed that Lactobacillus ramnose at a concentration of 10 μg/ml reduced the survival of HT-29 cells by 51.49±8.32%, and the coloring results detection showed that treatment of HT29 cells with Lactobacillus rhamnosis caused qualitative changes in cell apoptosis. Real-time PCR results showed that lactobacillus rhamnose bacteria significantly increased the expression of bax genes (4.2±0.22) and casp3 (6.88±0.92) compared to control gene in cancer cells of the HT29 colon (P<0.05).    Discussion & Conclusions: The results of this study showed that lactobacillus ramose bacteria increase the expression of bax, cas3 gene and cause induction of apoptosis in HT-29 cell line. 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بیوسنتز نانوذرات اکسیدروی توسط مواد درون سلولی مخمر ساکارومایسس سرویزیه(Saccharomyces cerevisiae) و بررسی خواص ضد باکتریایی و آنتی اکسیدانی آن Biosynthesis of Zinc Oxide Nanoparticles using Intracellular Extract of Saccharomyces cerevisiae and Evaluation of its Antibacterial and Antioxidant Activities 1 1 مقدمه: سنتز زیستی نانوذرات به عنوان یک فرآیند مقرون به صرفه، دوستدار محیط زیست و جایگزین روش های فیزیکی و شیمیایی مورد توجه قرار گرفته است. هدف از این پژوهش، سنتز نانوذرات اکسیدروی توسط مواد درون سلولی مخمر ساکارومایسس سرویزیه و بررسی اثرات ضدباکتریایی و آنتی اکسیدانی آن است. مواد و روش ها: در این مطالعه پس از تهیه نانوذرات و تعیین خصوصیات فیزیکی آن ها، اثر آنتی اکسیدانی نانوذرات توسط روش های مهار رادیکال آزاد DPPH (-diphenyl-1-picrylhydrazyl 2,2) و توانایی کاهندگی آهن سنجیده شد. فعالیت ضدباکتریایی نانوذرات با استفده از روش انتشار دیسک علیه باکتری های گرم مثبت از جمله استافیلوکوس اورئوس و لیستریا مونوسیتوژنز و باکتری گرم منفی اشیریشیاکلی بررسی شد. یافته های پژوهش: نانوذرات سنتز شده دارای مورفولوژی کروی و به طور میانگین، اندازه قطر آن ها کمتر از 30 نانومتر بود. پیک جذبی برجسته در 370 نانومتر بیانگر تشکیل نانوذرات اکسیدروی است. این نانوذرات دارای فعالیت ضدباکتریایی خوبی علیه باکتری استافیلوکوس اورئوس بوده و نیز فعالیت آنتی اکسیدانی وابسته به غلظت در هر دو روش نشان دادند. بحث و نتیجه گیری: نتایج مطالعه حاضر نشان داد که نانوذرات اکسیدروی سنتز شده دارای فعالیت ضدباکتریایی و آنتی اکسیدانی بوده و امکان کاربرد آن ها در بسته بندی مواد غذایی، لوازم آرایشی و نیز به عنوان جایگزین آنتی بیوتیک ها وجود داشته، لذا به مطالعات بیشتری در این زمینه نیاز است. 2 Introduction: Attention to the biosynthesis of nanoparticles (NPs) has been increased recently since they are cost-effective, eco-friendly, and potential alternatives to chemical and physical methods. This study aimed to synthesize zinc oxide nanoparticles (ZnO NPs) using an intracellular extract of Saccharomyces cerevisiae. Moreover, it was attempted to evaluate their antibacterial and antioxidant effects.   Materials & Methods: After the preparation and identification of the physical characteristics of the ZnO NPs, their antioxidant activity was determined using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and Ferric Reducing Ability of Plasma (FRAP). Moreover, the antibacterial activity of NPs was tested against Gram-positive bacteria (Staphylococcus aureus and Listeria monocytogenes) and Gram-negative bacteria (Escherichia coli) using a disc diffusion method. Ethics code: IR.ausmt.rec.1398.11.33 Findings: The results showed that the synthesized NPs had a spherical shape, and their diameter size was < 30 nm. A good absorption at 370 nm confirmed the presence of ZnO NPs. These NPs depicted an improved antibacterial activity against S. aureus. Moreover, they showed concentration-dependent antioxidant activity in both DPPH and FRAP.   Discussions & Conclusions: The results indicated that the biosynthesized ZnO NPs had antibacterial and antioxidant activities. This suggests that ZnO NPs can be used in food packaging and cosmetic products. In addition, they can be utilized as an alternative to synthetic antibiotics. However, further studies are required to be conducted in this regard. 36 46 2020/05/192019/12/182019/09/252020/02/5 1398/11/16 2020/09/162020/05/262020/04/282020/07/12 1399/4/22 راضیه معتضدی Razieh Motazedi گروه زیست فناوری میکروبی، دانشکده زیست فناوری، دانشگاه تخصصی فناوری های نوین آمل، آمل، ایران ایران motazedi70@gmail.com سمیه رهایی Somayeh Rahaiee گروه زیست فناوری میکروبی، دانشکده زیست فناوری، دانشگاه تخصصی فناوری های نوین آمل، آمل، ایران ایران s.rahaiee@ausmt.ac.ir محبوبه زارع Mahboobeh Zare گروه گیاهان دارویی، دانشکده گیاهان دارویی، دانشگاه تخصصی فناوری های نوین آمل، آمل، ایران ایران m.zare@ausmt.ac.ir ZnO NPs Biosynthesis Saccharomyces cerevisiae Antibacterial Antioxidant نانوذرات اکسیدروی سنتز زیستی ساکارومایسس سرویزیه ضدباکتریایی آنتی اکسیدانی Mala JGS, Rose C. Facile production of ZnS quantum dot nanoparticles by Saccharomyces cerevisiae MTCC 2918. J Biotechnol 2014; 170:73-8. doi:10.1016/ j.jbiotec.2013.11.017.##Benelmekki M. Designing hybrid nanoparticles. 2th ed. Morgan Claypool Publishing. 2015; P.231-9.doi. 10.1088/978-1-6270-5469-0.##Venkatesh N, Bhowmik H, Kuila A. Metallic nanoparticle a review. BJSTR 2018; 4: 3765-75. doi.10.26717/BJSTR.2018.04.001011.##Umamaheswari A, Lakshmana S, Puratchikody A. Biosynthesis of zinc oxide nanoparticle a review on greener approach. MOJBB 2018; 5: 151-4. doi.10.15406/ mojbb.2018.05.00096.##Jiang J, Pi J, Cai J. The advancing of zinc oxide nanoparticles for biomedical applications. Bioinorg Chem Appl 2018; 2018. doi.10.1155/2018/1062562.##Krol A, Pomastowski P, Rafinska K, Railean V, Buszewski B. Zinc oxide nanoparticles synthesis antiseptic activity and toxicity mechanism. Adv Coll Int Sci 2017; 249: 37-52. doi.10.1016/j.cis.2017.07.033.##Kolodziejczak A, Jesionowski T. Zinc oxide from synthesis to application a review. Materials 2014; 7: 2833-81. doi.10.3390/ma7042833.##Espitia PJP, Soares NDFF, Reis JS, Andrade NJ, Cruz RS, Medeiros EAA. Zinc oxide nanoparticles synthesis antimicrobial activity and food packaging applications. Food Bioproc Tech 2012; 5: 1447-64. doi.10.1007/s11947-012-0797-6.##Taran M, Rad M, Alavi M. Biosynthesis of TiO2 and ZnO nanoparticles by Halomonas elongata IBRC-M 10214 in different conditions of medium. Bio Impacts 2018; 8:81. doi.10.15171/bi.2018.10.##Das D, Nath B C, Phukon P, Dolui SK. Synthesis of ZnO nanoparticles and evaluation of antioxidant and cytotoxic activity. Coll Sur 2013; 111: 556-60 doi.10.1016/j.colsurfb.2013.06.041.##Khatami M, Alijani HQ, Heli H, Sharifi I. Rectangular shaped zinc oxide nanoparticles green synthesis by stevia and its biomedical efficiency. Ceram Int 2018; 44:15596-602. doi.10.1016/j.ceramint.2018.05.224##Begum S, Ahmaruzzaman M, Adhikari PP. Ecofriendly bio synthetic route to synthesize ZnO nanoparticles using eryngium foetidum L. and their activity against pathogenic bacteria. Mater Lett 2018; 228: 37-41. doi.10.1016/j.matlet.2018.05.091.##Iravani S. Bacteria in nanoparticle synthesis current status and future prospects. Int Sch Res Not 2014; 2:111-6. doi.10.1155/2014/359316.##Moghaddam AB, Moniri M, Azizi S, Rahim RA, Ariff AB, Saad WZ, et al. Biosynthesis of ZnO nanoparticles by a new Pichia kudriavzevii yeast strain and evaluation of their antimicrobial and antioxidant activities. Molecules 2017; 22: 872. doi. 10.3390/molecules22060872.##Basnet P, Chanu TI, Samanta D, Chatterjee, S. A review on bio synthesized zinc oxide nanoparticles using plant extracts as reductants and stabilizing agents. J Photochem Photobiol Biol 2018; 183: 201-21. doi.10.1016/j.jphotobiol.2018.04.036.##Jha AK, Prasad K, Prasad K. A green low cost biosynthesis of Sb2O3 nanoparticles. Biochem Eng J 2009; 43: 303-6. doi.10.1016/j.bej.2008.10.016.##Seyidoglu N, Peker S. Effects of different doses of probiotic yeast Saccharomyces cerevisiae on the duodenal mucosa in rabbits. Indian J Anim Res 2015; 49: 602-6. doi.10.18805/ijar.5570.##Korbekandi H, Mohseni S, Mardanijouneghani R, Pourhossein M, Iravani S. Biosynthesis of silver nanoparticles using Saccharomyces cerevisiae. Art Cell Nanomed Biotechnol 2016; 44: 235-9. doi.10.3109/21691401.2014.937870.##Ebadi M, Zolfaghari MR, Aghaei SS, Zargar M, Shafiei M, Zahiri HS, et al. A bio inspired strategy for the synthesis of zinc oxide nanoparticles using the cell extract of cyanobacterium Nostoc sp. EA03 from biological function to toxicity evaluation. Rsc Adv 2019; 9: 23508-25. doi.10.1039/C9RA03962G.##Erlandsen SL, Frethem C, Chen Y. Field emission scanning electron microscopy entering the 21st century nanometer resolution and molecular topography of cell structure. J Histotechnol 2000; 23: 249-59. doi.10.1179/his.2000.23.3.249.##‌21. Khan ZUH, Sadiq HM, Shah NS, Khan AU, Muhammad N, Hassan SU, et al. Greener synthesis of zinc oxide nanoparticles using Trianthema portulacastrum extract and evaluation of its photocatalytic and biological applications. J Photochem Photobiol Biol 2019; 192: 147-57. doi.10.1016/j.jphotobiol.2019.01.013.##Shobha N, Nanda N, Giresha AS, Manjappa P, Sophiya P, Dharmappa KK, Nagabhushana BM. Synthesis and characterization of Zinc oxide nanoparticles utilizing seed source of Ricinus communis and study of its antioxidant, antifungal and anticancer activity. Mate Sci Eng 2019; 97:842-50. doi.10.1016/j.msec.2018.12.023.##Shamim A, Abid MB, Mahmood T. Biogenic synthesis of Zinc oxide nanoparticles using a fungus Aspargillus niger and their characterization. Int. J Chem 2019; 11: 119-26. doi.10.5539/ijc.v11n2p119.##Jamdagni P, Khatri P, Rana JS. Green synthesis of zinc oxide nanoparticles using flower extract of Nyctanthes arbor tristis and their antifungal activity. J King Saud Uni Sci 2018; 30: 168-75. doi.10.1016/j.jksus.2016.10.00.2.##Reddy KM, Feris K, Bell J, Wingett DG, Hanley C, Punnoose A. Selective toxicity of zinc oxide nanoparticles to prokaryotic and eukaryotic systems. Appl Phys Lett 2007; 90: 213902. doi.10.1063/1.2742324.##Rajan A, Cherian E, Baskar G. Biosynthesis of zinc oxide nanoparticles using Aspergillus fumigatus JCF and its antibacterial activity. Int J Mod Sci Technol 2016; 1: 52-7.##Banerjee S, Saikia JP, Kumar A, Konwar BK. Antioxidant activity and haemolysis prevention efficiency of polyaniline nanofibers. J Nanotechnol 2009; 21: 45101.doi.10.1088/0957-4484/21/4/045101.##Madan HR, Sharma SC, Suresh D, Vidya YS, Nagabhushana H, Rajanaik H, et al. Facile green fabrication of nanostructure ZnO plates bullets flower prismatic tip closed pine cone their antibacterial antioxidant photoluminescent and photocatalytic properties. Acta Mol Biomol Spectrosc 2016; 152: 404-16. doi.10.1016/j.saa.2015.07.067.##Mala JGS, Rose C. Facile production of ZnS quantum dot nanoparticles by Saccharomyces cerevisiae MTCC 2918. J Biotechnol 2014; 170:73-8. doi:10.1016/ j.jbiotec.2013.11.017.##Benelmekki M. Designing hybrid nanoparticles. 2th ed. Morgan Claypool Publishing. 2015; P.231-9.doi. 10.1088/978-1-6270-5469-0.##Venkatesh N, Bhowmik H, Kuila A. Metallic nanoparticle a review. BJSTR 2018; 4: 3765-75. doi.10.26717/BJSTR.2018.04.001011.##Umamaheswari A, Lakshmana S, Puratchikody A. Biosynthesis of zinc oxide nanoparticle a review on greener approach. MOJBB 2018; 5: 151-4. doi.10.15406/ mojbb.2018.05.00096.##Jiang J, Pi J, Cai J. The advancing of zinc oxide nanoparticles for biomedical applications. Bioinorg Chem Appl 2018; 2018. doi.10.1155/2018/1062562.##Krol A, Pomastowski P, Rafinska K, Railean V, Buszewski B. Zinc oxide nanoparticles synthesis antiseptic activity and toxicity mechanism. Adv Coll Int Sci 2017; 249: 37-52. doi.10.1016/j.cis.2017.07.033.##Kolodziejczak A, Jesionowski T. Zinc oxide from synthesis to application a review. Materials 2014; 7: 2833-81. doi.10.3390/ma7042833.##Espitia PJP, Soares NDFF, Reis JS, Andrade NJ, Cruz RS, Medeiros EAA. Zinc oxide nanoparticles synthesis antimicrobial activity and food packaging applications. Food Bioproc Tech 2012; 5: 1447-64. doi.10.1007/s11947-012-0797-6.##Taran M, Rad M, Alavi M. Biosynthesis of TiO2 and ZnO nanoparticles by Halomonas elongata IBRC-M 10214 in different conditions of medium. Bio Impacts 2018; 8:81. doi.10.15171/bi.2018.10.##Das D, Nath B C, Phukon P, Dolui SK. Synthesis of ZnO nanoparticles and evaluation of antioxidant and cytotoxic activity. Coll Sur 2013; 111: 556-60 doi.10.1016/j.colsurfb.2013.06.041.##Khatami M, Alijani HQ, Heli H, Sharifi I. Rectangular shaped zinc oxide nanoparticles green synthesis by stevia and its biomedical efficiency. Ceram Int 2018; 44:15596-602. doi.10.1016/j.ceramint.2018.05.224##Begum S, Ahmaruzzaman M, Adhikari PP. Ecofriendly bio synthetic route to synthesize ZnO nanoparticles using eryngium foetidum L. and their activity against pathogenic bacteria. Mater Lett 2018; 228: 37-41. doi.10.1016/j.matlet.2018.05.091.##Iravani S. Bacteria in nanoparticle synthesis current status and future prospects. Int Sch Res Not 2014; 2:111-6. doi.10.1155/2014/359316.##Moghaddam AB, Moniri M, Azizi S, Rahim RA, Ariff AB, Saad WZ, et al. Biosynthesis of ZnO nanoparticles by a new Pichia kudriavzevii yeast strain and evaluation of their antimicrobial and antioxidant activities. Molecules 2017; 22: 872. doi. 10.3390/molecules22060872.##Basnet P, Chanu TI, Samanta D, Chatterjee, S. A review on bio synthesized zinc oxide nanoparticles using plant extracts as reductants and stabilizing agents. J Photochem Photobiol Biol 2018; 183: 201-21. doi.10.1016/j.jphotobiol.2018.04.036.##Jha AK, Prasad K, Prasad K. A green low cost biosynthesis of Sb2O3 nanoparticles. Biochem Eng J 2009; 43: 303-6. doi.10.1016/j.bej.2008.10.016.##Seyidoglu N, Peker S. Effects of different doses of probiotic yeast Saccharomyces cerevisiae on the duodenal mucosa in rabbits. Indian J Anim Res 2015; 49: 602-6. doi.10.18805/ijar.5570.##Korbekandi H, Mohseni S, Mardanijouneghani R, Pourhossein M, Iravani S. Biosynthesis of silver nanoparticles using Saccharomyces cerevisiae. Art Cell Nanomed Biotechnol 2016; 44: 235-9. doi.10.3109/21691401.2014.937870.##Ebadi M, Zolfaghari MR, Aghaei SS, Zargar M, Shafiei M, Zahiri HS, et al. A bio inspired strategy for the synthesis of zinc oxide nanoparticles using the cell extract of cyanobacterium Nostoc sp. EA03 from biological function to toxicity evaluation. Rsc Adv 2019; 9: 23508-25. doi.10.1039/C9RA03962G.##Erlandsen SL, Frethem C, Chen Y. Field emission scanning electron microscopy entering the 21st century nanometer resolution and molecular topography of cell structure. J Histotechnol 2000; 23: 249-59. doi.10.1179/his.2000.23.3.249.##‌21. Khan ZUH, Sadiq HM, Shah NS, Khan AU, Muhammad N, Hassan SU, et al. Greener synthesis of zinc oxide nanoparticles using Trianthema portulacastrum extract and evaluation of its photocatalytic and biological applications. J Photochem Photobiol Biol 2019; 192: 147-57. doi.10.1016/j.jphotobiol.2019.01.013.##Shobha N, Nanda N, Giresha AS, Manjappa P, Sophiya P, Dharmappa KK, Nagabhushana BM. Synthesis and characterization of Zinc oxide nanoparticles utilizing seed source of Ricinus communis and study of its antioxidant, antifungal and anticancer activity. Mate Sci Eng 2019; 97:842-50. doi.10.1016/j.msec.2018.12.023.##Shamim A, Abid MB, Mahmood T. Biogenic synthesis of Zinc oxide nanoparticles using a fungus Aspargillus niger and their characterization. Int. J Chem 2019; 11: 119-26. doi.10.5539/ijc.v11n2p119.##Jamdagni P, Khatri P, Rana JS. Green synthesis of zinc oxide nanoparticles using flower extract of Nyctanthes arbor tristis and their antifungal activity. J King Saud Uni Sci 2018; 30: 168-75. doi.10.1016/j.jksus.2016.10.00.2.##Reddy KM, Feris K, Bell J, Wingett DG, Hanley C, Punnoose A. Selective toxicity of zinc oxide nanoparticles to prokaryotic and eukaryotic systems. Appl Phys Lett 2007; 90: 213902. doi.10.1063/1.2742324.##Rajan A, Cherian E, Baskar G. Biosynthesis of zinc oxide nanoparticles using Aspergillus fumigatus JCF and its antibacterial activity. Int J Mod Sci Technol 2016; 1: 52-7.##Banerjee S, Saikia JP, Kumar A, Konwar BK. Antioxidant activity and haemolysis prevention efficiency of polyaniline nanofibers. J Nanotechnol 2009; 21: 45101.doi.10.1088/0957-4484/21/4/045101.##Madan HR, Sharma SC, Suresh D, Vidya YS, Nagabhushana H, Rajanaik H, et al. Facile green fabrication of nanostructure ZnO plates bullets flower prismatic tip closed pine cone their antibacterial antioxidant photoluminescent and photocatalytic properties. Acta Mol Biomol Spectrosc 2016; 152: 404-16. doi.10.1016/j.saa.2015.07.067.## ##

ارزشیابی برنامه آموزش بهداشت بر دانش، نگرش و رفتارهای پیشگیری کننده از تب مالت در روستائیان شهرستان هلیلان Evaluation of Health Education Program on Knowledge, Attitude, and Preventive Behaviors of Brucellosis among Villagers in Holilan, Iran 1 1 مقدمه: تب مالت معضلی بهداشتی است که سالانه صدمات اقتصادی-بهداشتی زیادی را برای جامعه در بر دارد. هدف این تحقیق بررسی تاثیر برنامه آموزشی بر دانش، نگرش و رفتارهای پیشگیری کننده از ابتلاء به تب مالت در جمعیت بخش هلیلان از توابع شهرستان چرداول، به منظور کاهش ابتلا به این بیماری است. مواد و روش ها: این مطالعه یک پژوهش نیمه تجربی است که به صورت قبل و بعد از آزمون انجام شد. جمعیت مورد مـــطالعه 209 نفر از مراجعه کنندگان به مراکز بهداشتی-درمانی منطقه هلیلان بود. نمونه ها به صورت تصادفی انتخاب شدند. ابزار جمع آوری داده ها پرسش نامه محقق ساخته بود که دانش، نگرش و رفتارهای پیشگیری کننده از تب مالت مورد سنجش قرار می گرفت. داده ها با استفاده از نرم افزار SPSS vol.16، و با انجام آزمون تی زوجی و کای اسکوئر در سطح معنی داری 05/0 مورد تجزیه و تحلیل قرار گرفت. یافته های پژوهش: میانگین سنی شرکت کنندگان 3/7±5/28 بود که 5/66 درصد از آن ها زن بودند. میانگین نمره دانش(P=0.001)، نگرش(P=0.025) و رفتارهای پیشگیری کننده(P=0.001) پس از مداخله آموزشی تفاوت معناداری با پیش آزمون داشتند. بحث و نتیجه گیری: این مطالعه نشان داد که برنامه آموزشی تدوین شده بر دانش، نگرش و رفتارهای پیشگیری کننده از ابتلاء به تب مالت در بین شرکت کننده گان تاثیرگذار بوده است. 2 Introduction: Brucellosis is a health problem that annually causes enormous economic and health damage to society. This study aimed to investigate the effect of an educational program on knowledge, attitude, and preventive behaviors of brucellosis in Holilan, Chardavol, Iran, to reduce the incidence of this disease.   Materials & Methods: This quasi-experimental study was conducted based on a pretest-posttest design. The study population included 209 cases who referred to the health centers in Holilan, Iran. The participants were selected randomly. Data were collected through a researcher-made questionnaire to measure knowledge, attitudes, and preventive behaviors of brucellosis among the participants. Data were analyzed using SPSS software (version16) through the paired t-test and Chi-square test. A p-value less than 0.05 was considered statistically significant.   Findings: The mean age of the participants was 28.5±7.3 years, 66.5% of whom were female. There was a significant difference between the pretest and posttest regarding the mean scores of knowledge (P=0.001), attitude (P=0.025), and preventive behaviors (P=0.001).   Discussion & Conclusions: The study showed the positive effect of the educational program on the knowledge, attitudes, and behaviors of the participants regarding brucellosis prevention. 47 53 2020/05/192019/12/182019/09/252020/02/52020/01/14 1398/10/24 2020/09/162020/05/262020/04/282020/07/122020/02/1 1398/11/12 اسفندیار عزیزی esfandiar azizi گروه ایمنی شناسی، دانشکده پزشکی، دانشگاه علوم پزشکی ایلام، ایلام، ایران ایران va.2010@yahoo.com مرتضی شمس Morteza Shams مرکز تحقیقات بیماری های زئونوز، دانشگاه علوم پزشکی ایلام، ایلام، ایران ایران علی صیدخانی نهال Ali Seidkhani گروه بیوشیمی، دانشکده پزشکی، دانشگاه علوم پزشکی ایلام، ایلام، ایران ایران seidkhani-a@medilam.ac.ir مرتضی حسین زاده Morteza hosseinzadeh گروه ایمنی شناسی، دانشکده پزشکی، دانشگاه علوم پزشکی ایلام، ایلام، ایران ایران Hosseinzadeh.m@medilam.ac.ir محسن جلیلیان Mohsen Jalilian گروه آموزش بهداشت، دانشکده بهداشت، دانشگاه علوم پزشکی ایلام، ایلام، ایران ایران jalilian91@yahoo.com صادق هواسی Sadegh Havasi گروه پزشکی اجتماعی، دانشکده پزشکی، دانشگاه علوم پزشکی ایلام، ایلام، ایران ایران va.1355@hotmail.com Attitude Behavior brucellosis Health education Knowledge آموزش بهداشت تب مالت دانش نگرش رفتار Franc KA, Krecek RC, Hasler BN, Arenas AM. Brucellosis remains a neglected disease in the developing world a call for interdisciplinary action. BMC Publ Health2018; 18:125. doi.10.1186/s12889-017-5016-y##Farahani S, Shahmohamadi S, Navidi I, Sofian M. [An investigation of the epidemiology of brucellosis in Arak city Iran 2001-2010]. HBIJ 2012; 14:49-54. (Persian)##Hatami H. Brucellosis epidemiology. 2th National Iranian Cong Bruce Shahid Beheshti Uni Med Sci Tehran Iran. 2007; P. 13-36.##Sawadkohi R, Siadati S, Zoughi E. [Evaluation of under 12 yearold patients with malta fever in Tehran children medical center and Amirkola children hospital Babol 1995-99]. J Mazandaran Uni Med Sci2001; 11:46-52. (Persian)##Babaei V, Garmaroodi GH, Batebi A, Alipour D, Shahbaz M, Babazadeh T. [The effectiveness of an educational intervention based on the health belief model in the empowerment of stockbreeders against high risk behaviors associated with brucellosis]. J Edu Commun Health2014; 1:12-9. (Persian)##Tyagita H, Mohdzamri S, Sitikhairani B, Shahrom S. Clinical human brucellosis in Malaysia: a case report. Asian Pac J Trop Dis 2014;4: 150-3.doi.10.1016/S2222-1808(14)60332-7##Panos A, Tsironib M, Spiros D, Athanassios A, Giorgos A. Acute brucellosis: presentation, diagnosis, and treatment of 144 cases. Int J Infect Dis2007; 11:52-7. doi.10.1016/j.ijid.2005.10.011##Eslami AA, Aligol M, Hafezibakhtiari M, Nasirzadeh M. [The effects of education on promoting knowledge, beliefs and preventive behaviors on brucellosis among Women applying a health belief model]. Jundishapur J Health Sci 2014; 6: 343-9. (Persian)##Hegazy Y, Elmonir W, Abdelhamid NH, Elbauomy EM. Seroprevalence and knowledge ttitudes and Practices survey of endemic ovine brucellosis in Egypt. Acta Vet Scand2016; 58:1.##Tebug SF, Kamga AR, Ema PJN, Muyeneza C, Kane O, Seck A, et al. Cattle farmer awareness and behavior regarding prevention of zoonotic disease transmission in Senegal. J Agromed 2015; 20:217-24. doi.10.1080/ 1059924X .2015.1010068.##Golshani M, Buozari S. A review of Brucellosis in Iran epidemiology risk factors diagnosis control and prevention. Iran Biomed J 2017; 21:349-59. doi.10.18869 /acadpub. ibj.21.6.349##Glanz K, Rimer BA, Viswanath K. Health behavior and Health education theory research and practice. 4th ed. John Wiley Son San Francisco Publication. 2008; p.265-9.##Pourhoseingholi MA, Vahedi M, Rahimzadeh M. Sample size calculation in medical studies. Gastroenterol Hepatol Bed Bench 2013; 6: 14–7.##Almasihashiani A, Khodayari M, Eshrati B, Shamsi M. [Factors affecting the interval between the onset and diagnosis of brucellosis in Markazi province Iran 2010-11]. Arak Med Sci Uni J2012; 14:21-30. (Persian)##Gharekhani J, Rasouli M, Abbasidoulatshahi E, Bahrami M, Hemati Z, Rezaei A. Seroepidemiological survey of brucellosis in small ruminants in Hamedan province Iran. J Adv Vet Anim Res2016; 3:399-405. doi. 0.5455/javar. 2016.c179##Rezaei H. [Effect of coding educational program on the knowledge attitude practice of animal husbandry women toward brucellosis in elected villages of Kangavar district]. J Tarbiat Modares Uni 2009; 2:23-9. (Persian)##Alahverdipour H, Bashirian S. [Brucellosis prevention program applying child to family health education method. Avice J Clin Med Sci 2010; 17: 46 -51.##Karimy M, Montazeri A, Araban M. [The effect of an educational program based on health belief model on the empowerment of rural women in prevention of brucellosis]. Arak Med Sci Uni J 2012; 2: 85-94. (Persian)##Baghianimoghadam MH, Hoseini N, Askari T. [A study of the knowledge attitude and practice of animal husbands about brucellosis in BahabadYazd]. J Sch Health Yazd 2016; 86:12-22. (Persian)##Zeng JY, Ciren DJ, Yundan DZ, Pu Q, Gongjue CW, Jiumei DJ, et al. A study of the knowledge, attitudes and practices of Tibetan yak herders with respect to brucellosis. Int Health 2018; 10:294–301. doi.10.1093/ inthealth/ihx076.##Sofian M. [Determination of Brucellosis model in Arak in 2005]. Arak Med Sci Uni J2006; 8:31-8. (Persian)##Hundal JS, Sodhi SS, Gupta A, Singh J, Chahal US. Awareness, knowledge and risks of zoonotic diseases among livestock farmers in Punjab. Vet World 2016; 9:186-91. doi.10.14202/vetworld.2015.186-191##Zhang N, Zhou H, Huang DS, Guan P. Brucellosis awareness and knowledge in communities worldwide: A systematic review and meta-analysis of 79 observational studies. PLos Negl Trop Dis 2019; 13:0007366-e. doi.10.1371/journal.pntd.0007366.##Franc KA, Krecek RC, Hasler BN, Arenas AM. Brucellosis remains a neglected disease in the developing world a call for interdisciplinary action. BMC Publ Health2018; 18:125. doi.10.1186/s12889-017-5016-y##Farahani S, Shahmohamadi S, Navidi I, Sofian M. [An investigation of the epidemiology of brucellosis in Arak city Iran 2001-2010]. HBIJ 2012; 14:49-54. (Persian)##Hatami H. Brucellosis epidemiology. 2th National Iranian Cong Bruce Shahid Beheshti Uni Med Sci Tehran Iran. 2007; P. 13-36.##Sawadkohi R, Siadati S, Zoughi E. [Evaluation of under 12 yearold patients with malta fever in Tehran children medical center and Amirkola children hospital Babol 1995-99]. J Mazandaran Uni Med Sci2001; 11:46-52. (Persian)##Babaei V, Garmaroodi GH, Batebi A, Alipour D, Shahbaz M, Babazadeh T. [The effectiveness of an educational intervention based on the health belief model in the empowerment of stockbreeders against high risk behaviors associated with brucellosis]. J Edu Commun Health2014; 1:12-9. (Persian)##Tyagita H, Mohdzamri S, Sitikhairani B, Shahrom S. Clinical human brucellosis in Malaysia: a case report. Asian Pac J Trop Dis 2014;4: 150-3.doi.10.1016/S2222-1808(14)60332-7##Panos A, Tsironib M, Spiros D, Athanassios A, Giorgos A. Acute brucellosis: presentation, diagnosis, and treatment of 144 cases. Int J Infect Dis2007; 11:52-7. doi.10.1016/j.ijid.2005.10.011##Eslami AA, Aligol M, Hafezibakhtiari M, Nasirzadeh M. [The effects of education on promoting knowledge, beliefs and preventive behaviors on brucellosis among Women applying a health belief model]. Jundishapur J Health Sci 2014; 6: 343-9. (Persian)##Hegazy Y, Elmonir W, Abdelhamid NH, Elbauomy EM. Seroprevalence and knowledge ttitudes and Practices survey of endemic ovine brucellosis in Egypt. Acta Vet Scand2016; 58:1.##Tebug SF, Kamga AR, Ema PJN, Muyeneza C, Kane O, Seck A, et al. Cattle farmer awareness and behavior regarding prevention of zoonotic disease transmission in Senegal. J Agromed 2015; 20:217-24. doi.10.1080/ 1059924X .2015.1010068.##Golshani M, Buozari S. A review of Brucellosis in Iran epidemiology risk factors diagnosis control and prevention. Iran Biomed J 2017; 21:349-59. doi.10.18869 /acadpub. ibj.21.6.349##Glanz K, Rimer BA, Viswanath K. Health behavior and Health education theory research and practice. 4th ed. John Wiley Son San Francisco Publication. 2008; p.265-9.##Pourhoseingholi MA, Vahedi M, Rahimzadeh M. Sample size calculation in medical studies. Gastroenterol Hepatol Bed Bench 2013; 6: 14–7.##Almasihashiani A, Khodayari M, Eshrati B, Shamsi M. [Factors affecting the interval between the onset and diagnosis of brucellosis in Markazi province Iran 2010-11]. Arak Med Sci Uni J2012; 14:21-30. (Persian)##Gharekhani J, Rasouli M, Abbasidoulatshahi E, Bahrami M, Hemati Z, Rezaei A. Seroepidemiological survey of brucellosis in small ruminants in Hamedan province Iran. J Adv Vet Anim Res2016; 3:399-405. doi. 0.5455/javar. 2016.c179##Rezaei H. [Effect of coding educational program on the knowledge attitude practice of animal husbandry women toward brucellosis in elected villages of Kangavar district]. J Tarbiat Modares Uni 2009; 2:23-9. (Persian)##Alahverdipour H, Bashirian S. [Brucellosis prevention program applying child to family health education method. Avice J Clin Med Sci 2010; 17: 46 -51.##Karimy M, Montazeri A, Araban M. [The effect of an educational program based on health belief model on the empowerment of rural women in prevention of brucellosis]. Arak Med Sci Uni J 2012; 2: 85-94. (Persian)##Baghianimoghadam MH, Hoseini N, Askari T. [A study of the knowledge attitude and practice of animal husbands about brucellosis in BahabadYazd]. J Sch Health Yazd 2016; 86:12-22. (Persian)##Zeng JY, Ciren DJ, Yundan DZ, Pu Q, Gongjue CW, Jiumei DJ, et al. A study of the knowledge, attitudes and practices of Tibetan yak herders with respect to brucellosis. Int Health 2018; 10:294–301. doi.10.1093/ inthealth/ihx076.##Sofian M. [Determination of Brucellosis model in Arak in 2005]. Arak Med Sci Uni J2006; 8:31-8. (Persian)##Hundal JS, Sodhi SS, Gupta A, Singh J, Chahal US. Awareness, knowledge and risks of zoonotic diseases among livestock farmers in Punjab. Vet World 2016; 9:186-91. doi.10.14202/vetworld.2015.186-191##Zhang N, Zhou H, Huang DS, Guan P. Brucellosis awareness and knowledge in communities worldwide: A systematic review and meta-analysis of 79 observational studies. PLos Negl Trop Dis 2019; 13:0007366-e. doi.10.1371/journal.pntd.0007366.## ##

اثر تمرین هوازی همراه با مکمل بربرین کلراید بر شاخص‌ های استرس اکسیداتیو بافت قلب موش‌ های دیابتی Effect of Aerobic Training and Berberine Chloride Supplementation on Oxidative Stress Indices in the Heart Tissue of Streptozotocin-Induced Diabetic Rats 1 1 هدف: استرس اکسیداتیو نقش مهمی در بروز و توسعه عوارض دیابت دارد. هدف از پژوهش حاضر بررسی اثر تمرین هوازی همراه با مصرف بربرین کلراید بر تغییرات شاخص ‌های استرس اکسیداتیو بافت قلب موش ‌های دیابتی با استرپتوزوتوسین بود. مواد و روش ‌ها: تعداد 32 موش صحرایی نر ویستار(03/17±09/276 گرم) به طور تصادفی به چـــهار گروه(8=n): دیــــابت(DM)، (59/65±18/277)، دیابت-بربرین(BDM)، (04/57±14/281)، دیابت-تمرین هوازی(TDM)، (14/38±12/262)، و دیابت-تمرین هوازی-بربرین (TBDM)، (05/78±17/282)، تقسیم شدند. دیابت با تزریق استرپتوزوتوسین در موش ‌های نر القا شد. گروه ‌های تمرین به مدت شش هفته برنامه تمرین هوازی فزاینده(18-10 متر در دقیقه، 40-10 دقیقه در روز، پنج روز در هفته) را روی تردمیل انجام دادند. در پایان هفته ششم نمونه بافت قلب جمع ‌آوری شده و برای بررسی آنزیم ‌های آنتی ‌اکسیدانی(شامل SOD، GPX و CAT) و سطح مالون ‌دی ‌آلدئید(MDA) استفاده شد. داده ها با استفاده از آزمون t مستقل و ANOVA در سطح معنی ‌داری P<0.05 آزمون شدند. یافته ‌های پژوهش: نتایج نشان داد که تمرین هوازی، بربرین و ترکیب تمرین-بربرین در موش ‌های دیابتی باعث افزایش معنی ‌دار در میزان SOD (P=0.001)، GPX (P=0.001) و CAT (P=0.001) بافت قلب شد. هم چنین افزایش معنی ‌داری در میزان این شاخص ‌ها در گروه TBDM نسبت به BDM و TDM مشاهده شد(P=0.05). میزان MDA در همه گروه ‌های تجربی نسبت به گروه دیابت کاهش معنی‌ داری داشت(P=0.001). بحث و نتیجه گیری: تمرین هوازی همراه با مصرف بربرین کلراید اثر مضاعفی بر بهبود نشانگر‌های استرس اکسیداتیو بافت قلب موش ‌های دیابتی با استرپتوزوتوسین دارد. 2 Introduction: Oxidative stress plays a key role in the onset and development of diabetes complications. This study aimed to investigate the effect of aerobic training with berberine chloride on indices changes of oxidative stress in the heart tissue of streptozotocin-induced diabetic rats.   Materials & Methods: In total, 32 male Wistar rats (276.09±17.03) were randomly divided into four groups of eight per group, including Diabetes (DM) (277.65±18.59), Diabetes-Berberine (BDM) (281.57±14.04), Diabetes-Aerobic Training (TDM) (262.38±12.14), and Diabetes-Aerobic Training-Berberine (TBDM) (282.78±17.05). Diabetes was induced by the injection of streptozotocin in male rats. The training groups performed a progressive aerobic running program (10-18 m/min, 10-40 min/day, and 5 days/week) on a motor-driven treadmill for six weeks. At the end of the sixth week, heart tissue specimens were collected and used for the determination of antioxidant enzymes (e.g., SOD, GPX, and CAT) and Malondialdehyde (MDA) level. The data were analyzed using independent t-test and ANOVA. A p-value less than 0.05 was considered statistically significant. Ethics code: IR.PNU.REC.1397.033   Findings: The results showed that aerobic training, berberine, and exercise-berberine combination significantly increased SOD (P=0.001), GPX (P=0.000), and CAT (P=0.001) of the heart tissue in diabetic rats. Moreover, a significant increase was observed in these indices in the TBDM group, compared to the BDM and TDM groups (P<0.05). The MDA level in all experimental groups was significantly lower than that in the diabetic group (P=0.001).   Discussions & Conclusions: Aerobic training combined with berberine chloride has remarkable interactive effects on the improvement of oxidative stress markers in the heart tissue of streptozotocin-induced diabetic rats. 54 65 2020/05/192019/12/182019/09/252020/02/52020/01/142019/11/10 1398/8/19 2020/09/162020/05/262020/04/282020/07/122020/02/12020/02/12 1398/11/23 عقیل صدیقی Aghil Sadighi گروه فیزیولوژی ورزشی، واحد آیت الله آملی، دانشگاه آزاد اسلامی، آمل، ایران ایران sady1365@gmail.com احمد عبدی Ahmad Abdi گروه فیزیولوژی ورزشی، واحد آیت الله آملی، دانشگاه آزاد اسلامی، آمل، ایران ایران a.abdi58@gmail.com محمدعلی آذربایجانی Mohammad Ali Azarbayjani گروه فیزیولوژی ورزشی، دانشکده تربیت بدنی و علوم ورزشی، واحد تهران مرکزی، دانشگاه آزاد اسلامی، تهران، ایران ایران ali.azarbayjani@gmail.com علیرضا براری Alireza Barari گروه فیزیولوژی ورزشی، واحد آیت الله آملی، دانشگاه آزاد اسلامی، آمل، ایران ایران alireza54.barari@gmail.com Berberine chloride Diabetes Exercise Oxidative stress فعالیت ورزشی بربرین کلراید دیابت استرس اکسیداتیو Farag YM, Gaballa MR. Diabesity an overview of a rising epidemic. Nephrol Dial Transplant 2011;26:28-35. doi.10.1093/ndt/gfq576.##Liu Q, Wang S, Cai L. Diabetic cardiomyopathy and its mechanisms: role of oxidative stress and damage. J Diabetes Investig 2014;5:623-34. doi.10.1111/jdi.12250.##Wang J, Song Y, Elsherif L, Song Z, Zhou G, Prabhu SD, et al. Cardiac metallothionein induction plays the major role in the prevention of diabetic cardiomyopathy by zinc supplementation. Circulation 2006; 113:544-54. doi:10.1161/circulationaha.105.537894.##Abdi A, Ramezani N, Abbasidaloie A, Ganji N. [The effect of aerobic training and coriandrum sativum extract on some oxidative stress factors in male diabetic wistar Rats]. Tabari J Prev Med 2017; 2:34-43. (Persian).##Ji L, Gomez M, Steinhafel N, Vina J. Acute exercise activates nuclear factor NF-κB signaling pathway in rat skeletal muscle. FASEB J 2004;18:1499-506. doi.10.1096/fj.04-1846com.##Ghyasi R, Mohaddes G, Naderi R. Combination effect of voluntary exercise and garlic (Allium sativum) on oxidative stress, cholesterol level and histopathology of heart tissue in type 1 diabetic Rats. J Cardiovasc Thorac Res 2019;11:61. doi.10.15171/jcvtr.2019.10.##Naderi R, Mohaddes G, Mohammadi M, Ghaznavi R, Ghyasi R, Vatankhah AM. Voluntary exercise protects heart from oxidative stress in diabetic Rats. Adv Pharm Bull 2015;5:231. d doi.10.15171/apb.2015.032.##Farzanegi P, Habibian M, Anvari SM. [Effect of swimming training and arbutin supplement on cardiac antioxidant enzymes and oxidative stress in diabetic Rats]. J Gorgan Uni Med Sci 2015;17:39-45. (Persian)##Judge S, Jang YM, Smith A, Selman C, Phillips T, Speakman JR, et al. Exercise by lifelong voluntary wheel running reduces subsarcolemmal and interfibrillar mitochondrial hydrogen peroxide production in the heart. Am J Physiol Reg Int Comp Physiol 2005;289: 1564-72. doi.10.1152/ajpregu.00396.2005.##Kazaz IO, Mentese A, Demir S, Kerimoglu G, Colak F, Bodur A, et al. Berberine inhibits the ischemia-reperfusion induced testicular injury through decreasing oxidative stress. Am J Eme Med 2020;38:33-37. doi.10.1016/j.ajem.2019.04.001.##Zhao GL, Yu LM, Gao WL, Duan WX, Jiang B, Liu XD, et al. Berberine protects rat heart from ischemia/reperfusion injury via activating JAK2/STAT3 signaling and attenuating endoplasmic reticulum stress. Acta Pharmacol Sin 2016;37:354-67. doi.10.1038/aps.2015.136.##Yu L, Li Q, Yu B, Yang Y, Jin Z, Duan W, et al. Berberine attenuates myocardial ischemia/reperfusion injury by reducing oxidative stress and inflammation response: role of silent information regulator 1. Oxid Med Cell Long 2016;2016:1689602. doi.10.1155/2016/1689602.##Seo H, Park CH, Choi S, Kim W, Jeon BD, Ryu S. Effects of voluntary exercise on apoptosis and cortisol after chronic restraint stress in mice. J Exerc Nutrition Biochem 2016;20:16. doi.10.20463/jenb.2016.09.20.3.3.##Høydal MA, Wisloff U, Kemi OJ, Ellingsen O. Running speed and maximal oxygen uptake in rats and mice: practical implications for exercise training. Eur J Cardiovasc Prev Rehabil 2007;14:753-60. doi: 10.1097/HJR.0b013e3281eacef1.##Mahmoud AM, Abdelrahman MM, Bastawy NA, Eissa HM. Modulatory effect of berberine on adipose tissue PPARγ, adipocytokines and oxidative stress in high fat diet/streptozotocin-induced diabetic Rats. JAPS 2017;7: -10. doi.10.7324/JAPS.2017.70401.##Servais S, Couturier K, Koubi H, Rouanet J, Desplanches D, Sornay M, et al. Effect of voluntary exercise on H2O2 release by subsarcolemmal and intermyofibrillar mitochondria. Free Rad Biol Med 2003;35:24-32. doi.10.1016/s0891-5849(03)00177-1.##Leeuwenburgh C, Hansen PA, Holloszy JO, Heinecke JW. Oxidized amino acids in the urine of aging rats: potential markers for assessing oxidative stress in vivo. Am J Physiol 1999;276: 128-35. doi: 10.1152/ajpregu.##Gimenes C, Gimenes R, Rosa C, Xavier N, Campos D, Fernandes A, et al. Low intensity physical exercise attenuates cardiac remodeling and myocardial oxidative stress and dysfunction in diabetic rats. J Diabetes Res 2015; 2015:457848. doi.10.1155/2015/457848.##Ghiasi R, Naderi R, Mozaffar A, Alihemmati A. The effect of swimming training on oxidative stress SIRT1 gene expression and histopathology of hepatic tissue in type 2 diabetic Rats. Biol Futura 2019; 70:167-74. doi.10.1556/019.70.2019.21.##Farhangi N, Nazem F, Zehsaz F. [Effect of endurance exercise on antioxidant enzyme activities and lipid peroxidation in the heart of the streptozotocin induced diabetic Rats]. JSSU 2017;24:798-809. (Persian)##Heyat F. [Cellular and Molecular Mechanisms of the production of free radicals during exercise and their function on skeletal muscles]. J Fasa Uni Med Sci 2017;7:1-11. (Persian)##Steinbacher P, Eckl P. Impact of oxidative stress on exercising skeletal muscle. Biomolecules 2015;5:356-77. doi.10.3390/biom5020356.##Toborek M, Seelbach MJ, Rashid CS, András IE, Chen L, Park M, et al. Voluntary exercise protects against methamphetamine induced oxidative stress in brain microvasculature and disruption of the blood brain barrier. Mole Neurodegener 2013; 8:22. doi.10.1186/1750-1326-8-22.##Kulkarni SK, Dhir A. Possible involvement of L-arginine-nitric oxide cyclic guanosine monophosphate signaling pathway in the antidepressant activity of berberine chloride. Eur J Pharmacol 2007;569:77-83. doi.10.1016/j.ejphar.2007.05.002.##Ju H, Li X, Zhao B, Han Z, Xin W. Scavenging effect of berbamine on active oxygen radicals in phorbol ester stimulated human polymorphonuclear leukocytes. Biochem Pharmacol 1990;39:1673-8. doi.10.1016/0006-2952(90)90110-7.##Kong WJ, Zhang H, Song DQ, Xue R, Zhao W, Wei J, et al. Berberine reduces insulin resistance through protein kinase C–dependent up regulation of insulin receptor expression. Metabolism 2009;58:109-19. doi.10.1016/j.metabol.2008.08.013.##Sharma B, Salunke R, Balomajumder C, Daniel S, Roy P. Anti-diabetic potential of alkaloid rich fraction from Capparis decidua on diabetic mice. J Ethnopharmacol 2010;127:457-62. doi.10.1016/j.jep.2009.10.013.##Zhang X, Ren H, Liu L. Effects of different dose berberine on hemodynamic parameters and Ca2+ i of cardiac myocytes of diastolic heart failure Rat model. Zhong Yao Za Zhi 2008;33:818-21.##Tan Y, Tang Q, HU Br, Xiang JZ. Antioxidant properties of berberine on cultured rabbit corpus cavernosum smooth muscle cells injured by hydrogen peroxide 1. Acta Pharmacol Sin 2007;28:1914-8. doi.10.1111/j.1745-7254.2007. 00705.x##Ezabadi A, Peeri M, Azarbayjani MA, Hosseini SA. The effects of resistance training and berberine chloride supplementation on oxidative stress markers in the cerebellum tissue of diazinon poisoned Rats. Middle East J Rehabil Health Stud20013; 6: 92870. doi.10.5812/mejrh.92870.##Farag YM, Gaballa MR. Diabesity an overview of a rising epidemic. Nephrol Dial Transplant 2011;26:28-35. doi.10.1093/ndt/gfq576.##Liu Q, Wang S, Cai L. Diabetic cardiomyopathy and its mechanisms: role of oxidative stress and damage. J Diabetes Investig 2014;5:623-34. doi.10.1111/jdi.12250.##Wang J, Song Y, Elsherif L, Song Z, Zhou G, Prabhu SD, et al. Cardiac metallothionein induction plays the major role in the prevention of diabetic cardiomyopathy by zinc supplementation. Circulation 2006; 113:544-54. doi:10.1161/circulationaha.105.537894.##Abdi A, Ramezani N, Abbasidaloie A, Ganji N. [The effect of aerobic training and coriandrum sativum extract on some oxidative stress factors in male diabetic wistar Rats]. Tabari J Prev Med 2017; 2:34-43. (Persian).##Ji L, Gomez M, Steinhafel N, Vina J. Acute exercise activates nuclear factor NF-κB signaling pathway in rat skeletal muscle. FASEB J 2004;18:1499-506. doi.10.1096/fj.04-1846com.##Ghyasi R, Mohaddes G, Naderi R. Combination effect of voluntary exercise and garlic (Allium sativum) on oxidative stress, cholesterol level and histopathology of heart tissue in type 1 diabetic Rats. J Cardiovasc Thorac Res 2019;11:61. doi.10.15171/jcvtr.2019.10.##Naderi R, Mohaddes G, Mohammadi M, Ghaznavi R, Ghyasi R, Vatankhah AM. Voluntary exercise protects heart from oxidative stress in diabetic Rats. Adv Pharm Bull 2015;5:231. d doi.10.15171/apb.2015.032.##Farzanegi P, Habibian M, Anvari SM. [Effect of swimming training and arbutin supplement on cardiac antioxidant enzymes and oxidative stress in diabetic Rats]. J Gorgan Uni Med Sci 2015;17:39-45. (Persian)##Judge S, Jang YM, Smith A, Selman C, Phillips T, Speakman JR, et al. Exercise by lifelong voluntary wheel running reduces subsarcolemmal and interfibrillar mitochondrial hydrogen peroxide production in the heart. Am J Physiol Reg Int Comp Physiol 2005;289: 1564-72. doi.10.1152/ajpregu.00396.2005.##Kazaz IO, Mentese A, Demir S, Kerimoglu G, Colak F, Bodur A, et al. Berberine inhibits the ischemia-reperfusion induced testicular injury through decreasing oxidative stress. Am J Eme Med 2020;38:33-37. doi.10.1016/j.ajem.2019.04.001.##Zhao GL, Yu LM, Gao WL, Duan WX, Jiang B, Liu XD, et al. Berberine protects rat heart from ischemia/reperfusion injury via activating JAK2/STAT3 signaling and attenuating endoplasmic reticulum stress. Acta Pharmacol Sin 2016;37:354-67. doi.10.1038/aps.2015.136.##Yu L, Li Q, Yu B, Yang Y, Jin Z, Duan W, et al. Berberine attenuates myocardial ischemia/reperfusion injury by reducing oxidative stress and inflammation response: role of silent information regulator 1. Oxid Med Cell Long 2016;2016:1689602. doi.10.1155/2016/1689602.##Seo H, Park CH, Choi S, Kim W, Jeon BD, Ryu S. Effects of voluntary exercise on apoptosis and cortisol after chronic restraint stress in mice. J Exerc Nutrition Biochem 2016;20:16. doi.10.20463/jenb.2016.09.20.3.3.##Høydal MA, Wisloff U, Kemi OJ, Ellingsen O. Running speed and maximal oxygen uptake in rats and mice: practical implications for exercise training. Eur J Cardiovasc Prev Rehabil 2007;14:753-60. doi: 10.1097/HJR.0b013e3281eacef1.##Mahmoud AM, Abdelrahman MM, Bastawy NA, Eissa HM. Modulatory effect of berberine on adipose tissue PPARγ, adipocytokines and oxidative stress in high fat diet/streptozotocin-induced diabetic Rats. JAPS 2017;7: -10. doi.10.7324/JAPS.2017.70401.##Servais S, Couturier K, Koubi H, Rouanet J, Desplanches D, Sornay M, et al. Effect of voluntary exercise on H2O2 release by subsarcolemmal and intermyofibrillar mitochondria. Free Rad Biol Med 2003;35:24-32. doi.10.1016/s0891-5849(03)00177-1.##Leeuwenburgh C, Hansen PA, Holloszy JO, Heinecke JW. Oxidized amino acids in the urine of aging rats: potential markers for assessing oxidative stress in vivo. Am J Physiol 1999;276: 128-35. doi: 10.1152/ajpregu.##Gimenes C, Gimenes R, Rosa C, Xavier N, Campos D, Fernandes A, et al. Low intensity physical exercise attenuates cardiac remodeling and myocardial oxidative stress and dysfunction in diabetic rats. J Diabetes Res 2015; 2015:457848. doi.10.1155/2015/457848.##Ghiasi R, Naderi R, Mozaffar A, Alihemmati A. The effect of swimming training on oxidative stress SIRT1 gene expression and histopathology of hepatic tissue in type 2 diabetic Rats. Biol Futura 2019; 70:167-74. doi.10.1556/019.70.2019.21.##Farhangi N, Nazem F, Zehsaz F. [Effect of endurance exercise on antioxidant enzyme activities and lipid peroxidation in the heart of the streptozotocin induced diabetic Rats]. JSSU 2017;24:798-809. (Persian)##Heyat F. [Cellular and Molecular Mechanisms of the production of free radicals during exercise and their function on skeletal muscles]. J Fasa Uni Med Sci 2017;7:1-11. (Persian)##Steinbacher P, Eckl P. Impact of oxidative stress on exercising skeletal muscle. Biomolecules 2015;5:356-77. doi.10.3390/biom5020356.##Toborek M, Seelbach MJ, Rashid CS, András IE, Chen L, Park M, et al. Voluntary exercise protects against methamphetamine induced oxidative stress in brain microvasculature and disruption of the blood brain barrier. Mole Neurodegener 2013; 8:22. doi.10.1186/1750-1326-8-22.##Kulkarni SK, Dhir A. Possible involvement of L-arginine-nitric oxide cyclic guanosine monophosphate signaling pathway in the antidepressant activity of berberine chloride. Eur J Pharmacol 2007;569:77-83. doi.10.1016/j.ejphar.2007.05.002.##Ju H, Li X, Zhao B, Han Z, Xin W. Scavenging effect of berbamine on active oxygen radicals in phorbol ester stimulated human polymorphonuclear leukocytes. Biochem Pharmacol 1990;39:1673-8. doi.10.1016/0006-2952(90)90110-7.##Kong WJ, Zhang H, Song DQ, Xue R, Zhao W, Wei J, et al. Berberine reduces insulin resistance through protein kinase C–dependent up regulation of insulin receptor expression. Metabolism 2009;58:109-19. doi.10.1016/j.metabol.2008.08.013.##Sharma B, Salunke R, Balomajumder C, Daniel S, Roy P. Anti-diabetic potential of alkaloid rich fraction from Capparis decidua on diabetic mice. J Ethnopharmacol 2010;127:457-62. doi.10.1016/j.jep.2009.10.013.##Zhang X, Ren H, Liu L. Effects of different dose berberine on hemodynamic parameters and Ca2+ i of cardiac myocytes of diastolic heart failure Rat model. Zhong Yao Za Zhi 2008;33:818-21.##Tan Y, Tang Q, HU Br, Xiang JZ. Antioxidant properties of berberine on cultured rabbit corpus cavernosum smooth muscle cells injured by hydrogen peroxide 1. Acta Pharmacol Sin 2007;28:1914-8. doi.10.1111/j.1745-7254.2007. 00705.x##Ezabadi A, Peeri M, Azarbayjani MA, Hosseini SA. The effects of resistance training and berberine chloride supplementation on oxidative stress markers in the cerebellum tissue of diazinon poisoned Rats. Middle East J Rehabil Health Stud20013; 6: 92870. doi.10.5812/mejrh.92870.## ##

بررسی وضعیت بیان و متیلاسیون پروموتر ژن ELF5 در بیماران مبتلا به سرطان پستان Investigation of Expression and Methylation Status of ELF5 Gene Promoter in Patients with Breast Cancer 1 1 مقدمه: سرطان پستان شایع ترین نوع سرطان در زنان ایرانی است. ژنELF5  به عنوان یک  فاکتور رونویسی از خانوادهETS  می تواند نقش کلیدی در بدخیمی سرطان پستان خصوصاً در زیر گروهbasal-like  و فرم های مقاوم آندوکرینی ایفا نماید. تغییرات متیلاسیون پروموتر ژن، هدف مناسبی جهت اســــتراتژی های درمــانی  محسوب می شود. در مطالعه حاضر فراوانی این پدیده اپیژنتیک و بیان ژن ELF5 و نیز ارتباط آن ها با ویژگی های پاتولوژیکی و بالینی بیماران ایرانی مبتلا به سرطان پستان مورد بررسی قرار گرفت. مواد و روش ها: در مطالعه حاضر به منظور بررسی متیلاسیون پروموتر ژن ELF5، 134 نمونه بافـــتی با استــــفاده از روش  Methylation Specific PCR و جهت بررسی بیان ژن، 164 نمونه بافتی توموری و 10 نمونه بافت نرمال پستانی مستخرج از جراحی زیبایی کاهش حجم پستان با استفاده از روش Real-Time RT-PCR مورد بررسی قرار گرفتند. یافته های پژوهش: داده های حاصل از این پژوهش مبین این امر است که حدود 70 درصد از نمونه های بافت بیماران مبتلا به سرطان پستان در ناحیه پروموتر ژن ELF5 واجد متیلاسیون می باشند. هم چنین کاهش بیان ژن ELF5 با افزایش استیج یا مرحله بیماری، سه گانه منفی بودن و تهاجم ارتباط معناداری را نشان می دهد. بحث و نتیجه گیری: نتایج حاضر مبین این است که افزایش فراوانی متیلاسیون پروموتر این ژن در بیماران نسبت به بافت های کنترل و ارتباط آن با عوامل موید پروگنوز ضعیف بیماری می تواند به عنوان یک کاندید احتمالی جهت مطالعات بیشتر در جهت تایید نقش زیست نشانگر پیش اگهی ضعیف در سرطان پستان معرفی گردد.   2 Introduction: Breast cancer is the most prevalent cancer among Iranian women. ELF5 gene as a transcription factor member of the ETS family could play a key role in breast cancer neoplasms, especially basal-like and endocrine-resistant subtypes. The changes in the gene promoter methylation pattern are considered proper targets in the therapeutic strategies. This study aimed to investigate the frequency of this epigenetic phenomenon and ELF5 gene expression as well as their association with pathologic and clinical characteristics of Iranian patients suffering from this cancer.   Materials & Methods: In order to investigate the ELF5 promoter methylation, 134 breast tissues were analyzed using methylation-specific PCR method. Moreover, 164 tumoral and 10 normal breast tissues retrieved from breast reduction surgery were assessed using Real-Time RT-PCR to analyze the gene expression. Ethics code: 52d/4922, 6.10.2016   Findings: The data revealed that about 70% of the breast cancer tumoral specimens showed ELF5 promoter methylated pattern. Furthermore, the down-regulation of ELF5 gene expression was significantly associated with higher cancer stages, being triple-negative, and invasion.   Discussions & Conclusions: The results revealed that an increase in the ELF5 promoter methylation frequency in patients, compared to the control tissues, and its association with poor prognosis indicators may propose the ELF5 promoter methylation as a possible candidate in further studies to confirm the poor prognostic role of this biomarker in breast cancer. 66 78 2020/05/192019/12/182019/09/252020/02/52020/01/142019/11/102019/09/15 1398/6/24 2020/09/162020/05/262020/04/282020/07/122020/02/12020/02/122020/04/14 1399/1/26 آذر حیدری زادی Azar Heidarizadi گروه ژنتیک، واحد علوم و تحقیقات فارس، دانشگاه آزاد اسلامی، مرودشت، ایران ایران azar.heidarizadi@gmail.com مهدیه سلیمی Mahdieh Salimi گروه ژنتیک پزشکی، پژوهشکده زیست فناوری پزشکی، پژوهشگاه ملی مهندسی ژنتیک و زیست فناوری، تهران، ایران ایران salimi@nigeb.ac.ir حسین مزدارانی Hossein Mozdarani گروه ژنتیک پزشکی، دانشکده پزشکی، دانشگاه تربیت مدرس، تهران، ایران ایران MOZDARAH@modaress.ac.ir Breast neoplasms ELF5 Epigenetics Gene expression Methylation ELF5 متیلاسون سرطان پستان بیان ژن اپی ژنتیک Mousavi SM, Montazeri A, Mohagheghi MA, Jarrahi AM, Harirchi I, Najafi M, Ebrahimi M. Breast cancer in Iran an epidemiological review. Breast J 2007; 13:383-91. doi.10.1111/j.1524-474##Dumitrescu RG. Early epigenetic markers for precision medicine. Meth Mol Biol 2018; 1856:3-17. doi.10.1007/978-1-4939-8751-1-1.##Ramalho J, Henrique R, Jeronimo C. Methylation specific PCR in Tost J DNA methylation protocols. Meth Mole Biol2018; 1708:123-9. doi.10.1007/978-1-4939-7481-8-23##Abbasi B, Ansarinejad N, Fardad F, Nasiripour S, Ramim T. [Breast cancer epigenetics]. Tehran Uni Med J 2016; 74:535-44. (Persian)##Brancaccio M, Natale F, Falco G, Angrisano T. Cell free DNA methylation the new frontiers of pancreatic cancer biomarkers discovery. Genes2020; 11:14. doi.10.3390/genes11010014##Lee HJ, Hinshelwood RA, Bouras T, Gallego D, Valdes F, Blazek K, et al. Lineage specific methylation of the Elf5 promoter in mammary epithelial cells. Stemcells 2011; 29:1611-9. doi.10.1002/stem.706##Zhang X, Lin J, Ma Y, Zhao J. Overexpression of E74-like factor 5 inhibits migration and invasion of ovarian cancer cells. Int J Exp Clin Res2019; 25:856. doi.10.12659/MSM.913058##Luk IY, Reehorst CM, Mariadason JM. ELF3 and ELF5 and EHF and SPDEF transcription factors in tissue homeostasis and cancer. Molecules 2018; 23:2191. doi.10.3390/molecules23092191##Zhou J, Ng AY, Tymms MJ, Jermiin LS, Seth AK, Thomas RS, et al. A novel transcription factor ELF5 belongs to the ELF subfamily of ETS genes and maps to human chromosome 11p13–15 a region subject to LOH and rearrangement in human carcinoma cell lines. Oncogene 1998; 17:2719-32. doi.10.1038/sj.onc.1202198##Omata F, Mcnamara KM, Suzuki K, Abe E, Hirakawa H, Ishida T, et al. Effect of the normal mammary differentiation regulator ELF5 upon clinical outcomes of triple negative breast cancers patients. Breast Cancer2018 1; 25:489-96. doi.10.1007/s12282-018-0842-z.##Lapinskas EJ, Svobodova S, Davis ID, Cebon J, Hertzog PJ, Pritchard MA. The ets transcription factor elf5 functions as a tumor suppressor in the kidney. Twin Res Hum Gene2011; 14:316-22. doi.10.1375/twin.14.4.316.##Metzger DE, Xu Y, Shannon JM. Elf5 is an epithelium specific fibroblast growth factor sensitive transcription factor in the embryonic lung. Dev Dynam Off Publ Am Associ Anatom2007; 236:1175-92. doi.10.1002/dvdy.21133.##Chakrabarti R, Hwang J, Blanco MA, Wei Y, Lukacisin M, Romano RA, et al. Elf5 inhibits the epithelial mesenchymal transition in mammary gland development and breast cancer metastasis by transcriptionally repressing Snail2. Nature Cell Biol2012; 14:1212-22. doi.10.1038/ncb2607.##Wu B, Cao X, Liang X, Zhang X, Zhang W, Sun G, et al. Epigenetic regulation of Elf5 is associated with epithelial-mesenchymal transition in urothelial cancer. Plos One2015 28;10: 117510. doi.10.1371/journal.pone.0117510.##Rogers RL, Seuningen I, Gould J, Hertzog PJ, Naylor MJ, Pritchard MA. Transcript profiling of Elf5+/− mammary glands during pregnancy identifies novel targets of Elf5. Plos One 2010 7; 5: 13150. doi.10.1371/journal.pone.0013150.##Furth PA, Nakles RE, Millman S, Diaz ES, Cabrera MC. Signal transducer and activator of transcription 5 as a key signaling pathway in normal mammary gland developmental biology and breast cancer. Breast Cancer Res Ac2011; 13:220. doi.10.1186/bcr2921.##Chean J, Chen CJ, Shively JE. ETS transcription factor ELF5 induces lumen formation in a 3D model of mammary morphogenesis and its expression is inhibited by Jak2 inhibitor TG101348. ExpCell Res2017; 359:62-75. doi.10.1016/j.yexcr.2017.08.008.##Siegel PM, Muller WJ. Transcription factor regulatory networks in mammary epithelial development and tumorigenesis. Oncogene2010; 29:2753-9. doi.10.1038/onc.2010.43.##Piggin CL, Roden DL, Gallego D, Lee HJ, Oakes SR, Ormandy CJ. ELF5 isoform expression is tissue specific and significantly altered in cancer. Breast Cancer Res2016; 18:4. doi.10.1186/s13058-015-0666-0.##Okamura Y, Aoki Y, Obayashi T, Tadaka S, Ito S, Narise T, et al. Coexpression database for animal species by DNA-microarray and RNAseq based expression data with multiple quality assessment systems. Nucle Acids Res2015; 43: 82-6. doi.10.1093/nar/gku1163.##Fitzgerald LM, Browne EP, Christie KD, Punska EC, Simmons LO, Williams KE, et al. ELF5 and dok7 regulation in anti-estrogen treated cells and tumors. Cancer Cell Int2016; 16:8. doi.10.1186/s12935-016-0282-9.##Mathsyaraja H, Ostrowski MC. Setting Snail2s pace during EMT. Nature Cell Biolo 2012; 14:123-7. doi.10.1038/ncb2616##Mousavi SM, Montazeri A, Mohagheghi MA, Jarrahi AM, Harirchi I, Najafi M, Ebrahimi M. Breast cancer in Iran an epidemiological review. Breast J 2007; 13:383-91. doi.10.1111/j.1524-474##Dumitrescu RG. Early epigenetic markers for precision medicine. Meth Mol Biol 2018; 1856:3-17. doi.10.1007/978-1-4939-8751-1-1.##Ramalho J, Henrique R, Jeronimo C. Methylation specific PCR in Tost J DNA methylation protocols. Meth Mole Biol2018; 1708:123-9. doi.10.1007/978-1-4939-7481-8-23##Abbasi B, Ansarinejad N, Fardad F, Nasiripour S, Ramim T. [Breast cancer epigenetics]. Tehran Uni Med J 2016; 74:535-44. (Persian)##Brancaccio M, Natale F, Falco G, Angrisano T. Cell free DNA methylation the new frontiers of pancreatic cancer biomarkers discovery. Genes2020; 11:14. doi.10.3390/genes11010014##Lee HJ, Hinshelwood RA, Bouras T, Gallego D, Valdes F, Blazek K, et al. Lineage specific methylation of the Elf5 promoter in mammary epithelial cells. Stemcells 2011; 29:1611-9. doi.10.1002/stem.706##Zhang X, Lin J, Ma Y, Zhao J. Overexpression of E74-like factor 5 inhibits migration and invasion of ovarian cancer cells. Int J Exp Clin Res2019; 25:856. doi.10.12659/MSM.913058##Luk IY, Reehorst CM, Mariadason JM. ELF3 and ELF5 and EHF and SPDEF transcription factors in tissue homeostasis and cancer. Molecules 2018; 23:2191. doi.10.3390/molecules23092191##Zhou J, Ng AY, Tymms MJ, Jermiin LS, Seth AK, Thomas RS, et al. A novel transcription factor ELF5 belongs to the ELF subfamily of ETS genes and maps to human chromosome 11p13–15 a region subject to LOH and rearrangement in human carcinoma cell lines. Oncogene 1998; 17:2719-32. doi.10.1038/sj.onc.1202198##Omata F, Mcnamara KM, Suzuki K, Abe E, Hirakawa H, Ishida T, et al. Effect of the normal mammary differentiation regulator ELF5 upon clinical outcomes of triple negative breast cancers patients. Breast Cancer2018 1; 25:489-96. doi.10.1007/s12282-018-0842-z.##Lapinskas EJ, Svobodova S, Davis ID, Cebon J, Hertzog PJ, Pritchard MA. The ets transcription factor elf5 functions as a tumor suppressor in the kidney. Twin Res Hum Gene2011; 14:316-22. doi.10.1375/twin.14.4.316.##Metzger DE, Xu Y, Shannon JM. Elf5 is an epithelium specific fibroblast growth factor sensitive transcription factor in the embryonic lung. 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اثر تمرین تناوبی شدید به دنبال ایسکمی-خون رسانی مجدد عضله قلب بر بیان ژن hand2و PI3K پلاسما موش ‌های صحرایی Effect of High-Intensity Interval Training following Ischemia-Reperfusion Injury in Heart on Hand 2 and Phosphatidylinositol-3-Kinase Genes in Male Rats 1 1 مقدمه: پژوهش های بالینی و هم چنین تجربی نشان داده­ اند برنامه ورزشی یکی از موثرترین راهبردهای کاهش پیشرفت کاردیومیوپاتی و کاهش دهنده بروز عوارض قلبی عروقی و مرگ و میرهای ناشی از ایسکمی میوکارد است. این مطالعه با هدف بررسی نقش تمرین تناوبی شدید بر بیان ژن  hand2و فسفاتیدیل اینوزیتول-3-کیناز پلاسما در رت های ایسکمی قلبی شده صورت گرفت. مواد و روش ها: در این مطالعه 28 سر موش صحرایی نر نژاد ویستار(250-200 گرم) به صورت تصادفی در 4 گروه شم، ایسکمی، تمرین و تمرین-ایسکمی قرار گرفتند. انفارکتوس میوکارد با بستن شریان کرونری نزولی چپ به مدت 30 دقیقه انجام شد. برنامه تمرینی اینتروال شدید(هر تناوب شامل 4 دقیقه دویدن با شدت خیلی بالا، تقریباً 85 تا 90 درصد VO2max و 2 دقیقه ریکاوری فعال، تقریباً با شدت 50 تا 60 درصد VO2max) روی تردمیل به مدت 8 هفته هر هفته 3 روز و هر روز  به مدت 40 دقیقه اجرا شد. یافته های پژوهش: نتایج نشان داد که سطح بیان ژن Hand2 در گروه تمرین-ایسکمی افزایش معناداری به نسبت گروه شم(P=0.001) و ایسکمی(P=0.001) داشت. هم چنین میزان غلظت فسفاتیدیل اینوزیتول-3-کیناز(PI3K) در گروه های تمرین، تمرین-ایسکمی افزایش معناداری به نسبت گروه های شم(P=0.001) و ایسکمی(P=0.001) داشت، اما در گروه ایسکمی به نسبت سایر گروه ها کاهش معناداری یافت(P<0.05). بحث و نتیجه گیری: یافته های پژوهش حاضر به طور کلی نشان داد که تمرین تناوبی شدید منجر به افزایش بیان ژن hand2 و pi3k می شود و در واقع تمرین تناوبی شدید منجر به هایپرتروفی فیزیولوژیک می شود و از طرفی دیگر در هایـــپرتروفی پاتولوژیک این متغیرها کاهش می یابند. 2 Introduction: Experimental and clinical studies have shown that exercise training is one of the most effective strategies for reducing the progression of cardiomyopathy and decreasing the incidence of cardiovascular complications and mortality due to myocardial ischemia. This study aimed to investigate the role of high-intensity interval training (HIIT) in the expression of Hand2 and Phosphatidylinositol-3-kinase (PI3K) genes in cardiac ischemia rats.   Materials & Methods: In this study, 28 male Wistar rats (200-250 g) were randomly divided into four groups of sham, ischemia, exercise, and exercise-ischemia. Myocardial infarction was performed by the closure of the left anterior descending artery for 30 min. In total, 40-min HIIT (each interval consisted of 4-min very high intensity running with approximately 85% to 90% maximum rate of oxygen consumption [VO2max] followed by 2-min active recovery with approximately 50% to 60% VO2max) were performed three days a week for eight weeks.  Ethics code: IR.SSRI.REC.1396.134   Findings: The results showed that the expression level of the Hand2 gene in the ischemia-training group was significantly increased, compared to the sham (P=0.001) and ischemia (P=0.001) groups. Furthermore, the concentration of PI3K in the exercise and exercise-ischemia groups was significantly increased, compared to the sham (P=0.001) and ischemia (P=0.001) groups. However, there was a decrease in the ischemia group, compared to the other groups (P<0.05).   Discussions & Conclusions: The findings of the present study showed that HIIT leads to increased expression of the Hand2 gene and PI3K. Furthermore, the HIIT results in physiological hypertrophy. On the other hand, the pathological hypertrophy of these variables is reduced in this study. 79 89 2020/05/192019/12/182019/09/252020/02/52020/01/142019/11/102019/09/152019/11/3 1398/8/12 2020/09/162020/05/262020/04/282020/07/122020/02/12020/02/122020/04/142020/04/19 1399/1/31 علی حیدریان پور Ali Heidarianpour گروه فیزیولوژی ورزشی، دانشکده علوم ورزشی، دانشگاه بوعلی سینا همدان، همدان، ایران ایران Heidarian317@gmail.com یعقوب مهری الوار Yaghoub Mehrialvar گروه فیزیولوژی ورزشی، دانشکده علوم ورزشی، دانشگاه بوعلی سینا همدان، همدان، ایران ایران yaghoob.alvar@ut.ac.ir شیوا مهری الوار Shiva Mehrialvar گروه فیزیولوژی ورزشی، دانشکده علوم ورزشی، دانشگاه بوعلی سینا همدان، همدان، ایران ایران sh.mehrialvar@gmail.com Exercise training Myocardial ischemia Pathological hypertrophy Physiological hypertrophy Phosphatidylinositol-3-kinase هایپرتروفی پاتولوژیک ایسکمی میوکارد هایپرتروفی فیزیولوژیک تمرین ورزشی فسفاتیدیل اینوزیتول-3-کیناز Tao L, Bei Y, Zhang H, Xiao J, Li X. Exercise for the heart signaling pathways. Oncotarget 2015; 6:20773. doi.10.18632/oncotarget.4770##Pluim B, Zwinderman AH, Laarse A, Wall EE. The athletes heart a meta-analysis of cardiac structure and function. Circulation 2000; 101:336-44. doi. 10.1161/ 01.cir.101.3.336##Palabiyik O, Tastekin E, Doganlar ZB, Tayfur P, Dogan A, Vardar SA. Alteration in cardiac PI3K/Akt/mTOR and ERK signaling pathways with the use of growth hormone and swimming and the roles of miR21 and miR133. Biomed Rep2019; 10:97-106. doi. 10.3892/br.2018.1179##Sanada S, Komuro I, Kitakaze M. Pathophysiology of myocardial reperfusion injury preconditioning, postconditioning and translational aspects of protective measures. Am J Heart Circul Physio l2011;301: 723-41. doi. 10.1152/ ajpheart. 00553.2011##Lloyd D, Adams RJ, Brown TM, Carn-ethon M, Dai S, Simone G, et al. Executive summary heart disease and stroke statistics 2010 update a report from the American heart association. Circulation 2010; 121: 948-54. doi.10.1161/CIR. 0000000000000 757##Whitcomb J, Gharibeh L, Nemer M. From embryogenesis to adulthood critical role for GATA factors in heart development and function. IUBMB Life2019; 2:81-6. doi.10.1002/iub.2163##George R, Firulli AB. Hand factors in cardiac development. Anatom Rec2019; 302:101-7. doi: 10.1002/ar.23910##Beisvag V, Kemi OJ, Arbo I, Loennechen JP, Wisloff U, Langaas M. Pathological and physiological hypertrophies are regulated by distinct gene programs. European J Car-diovasPreve Rehabil2009; 16:690-7. doi. 10.1097/HJR.0b013e32833158a2##Lu C, Gong HR, Liu XY, Wang J, Zhao CM, Huang RT. A novel HAND2 loss-of-function mutation responsible for tetralogy of Fallot. Int J Mole Med2016; 37:445-51. doi.10.3892/ijmm.2015.2436##Gharaat M, Kashef M, Jameie B, Rajabi H. [Effect of endurance a nd high intensity interval swimming training on cardiac structure and Hand2 expression of Rats]. SSUJ 2017; 25:748-58.##Lu K, Wang L, Wang C, Yang Y, Hu D, Ding R. Effects of high intensity interval versus continuous moderate intensity aerobic exercise on apoptosis, oxidative stress and metabolism of the infarcted myocardium in a Rat model. Mole Med Rep 2015; 12:2374-82. doi.10.4103/ jrms.JRMS_292_18##Fathi M, Gharakhanlou R. [Effect of Endurance training on Hand2 gene expression in left ventricle of male Rats]. Sport Physiol 2015; 7: 57-68. (Persian)##Shioi T, Kang PM, Douglas PS, Hampe J, Yballe CM, Lawitts J. The conserved phosphoinositide 3‐kinase pathway determ-ines heart size in Mice. EMBO J2000; 19:2537-48. doi.10.1093/emboj/ 19.11.2537##Huenges K, Pokorny S, Berndt R, Cremer J, Lutter G. Transesophageal echocardiography in swine establishment of a baseline. Ult Med Biol2017; 43:974-80. doi.10.1016/j.ultrasmedbio.2016.12.011##Hoydal M, Wisloff U, Kemi OJ, Ellin-gsen O. Running speed and maximal oxy-gen uptake in rats and Mice practical imp-lications for exercise training. European J Cardiovas Preve Rehabil2007; 4:753-60. doi.10.1097/HJR.0b013e3281eacef1##Wisloff U, Loennechen JP, Currie S, Smith GL, Ellingsen O. Aerobic exercise reduces cardiomyocyte hypertrophy and increases contractility Ca2+ sensitivity and SERCA-2 in rat after myocardial infarction. Cardiovas Res2002;54: 162-74.doi.10. 1016/s0008-6363(01)00565-x##Sun Y, Wang J, Qiu XB, Yuan F, Li RG, Xu YJ, et al. A HAND2 loss of function mutation causes familial ventricular septal defect and pulmonary stenosis. Gen Genom Genet 2016; 6:987-92. doi.10.1534/g3. 115.026518##O'Neill B, Kim J, Wende AR, Theobald HA, Tuinei J, Buchanan J, Guo A, Zaha VG, Davis DK, Schell JC, Boudina S. A conserved role for phosphatidylinositol 3-kinase but not Akt signaling in mitochon-drial adaptations that accompany physiol-ogical cardiac hypertrophy. Cell Metab 2007; 6:294-306. doi. 10.1016/ j.cmet. 2007.09.001##Owen K, Pretorius L, McMullen JR. The protective effects of exercise and phosphor-inositide 3-kinase p110α in the failing heart. Clin Sci2009; 116:365-75. doi.10. 1042/CS20080183##Tao L, Bei Y, Zhang H, Xiao J, Li X. Exercise for the heart signaling pathways. Oncotarget 2015; 6:20773. doi.10.18632/oncotarget.4770##Pluim B, Zwinderman AH, Laarse A, Wall EE. The athletes heart a meta-analysis of cardiac structure and function. Circulation 2000; 101:336-44. doi. 10.1161/ 01.cir.101.3.336##Palabiyik O, Tastekin E, Doganlar ZB, Tayfur P, Dogan A, Vardar SA. Alteration in cardiac PI3K/Akt/mTOR and ERK signaling pathways with the use of growth hormone and swimming and the roles of miR21 and miR133. Biomed Rep2019; 10:97-106. doi. 10.3892/br.2018.1179##Sanada S, Komuro I, Kitakaze M. Pathophysiology of myocardial reperfusion injury preconditioning, postconditioning and translational aspects of protective measures. Am J Heart Circul Physio l2011;301: 723-41. doi. 10.1152/ ajpheart. 00553.2011##Lloyd D, Adams RJ, Brown TM, Carn-ethon M, Dai S, Simone G, et al. Executive summary heart disease and stroke statistics 2010 update a report from the American heart association. Circulation 2010; 121: 948-54. doi.10.1161/CIR. 0000000000000 757##Whitcomb J, Gharibeh L, Nemer M. From embryogenesis to adulthood critical role for GATA factors in heart development and function. IUBMB Life2019; 2:81-6. doi.10.1002/iub.2163##George R, Firulli AB. Hand factors in cardiac development. Anatom Rec2019; 302:101-7. doi: 10.1002/ar.23910##Beisvag V, Kemi OJ, Arbo I, Loennechen JP, Wisloff U, Langaas M. Pathological and physiological hypertrophies are regulated by distinct gene programs. European J Car-diovasPreve Rehabil2009; 16:690-7. doi. 10.1097/HJR.0b013e32833158a2##Lu C, Gong HR, Liu XY, Wang J, Zhao CM, Huang RT. A novel HAND2 loss-of-function mutation responsible for tetralogy of Fallot. Int J Mole Med2016; 37:445-51. doi.10.3892/ijmm.2015.2436##Gharaat M, Kashef M, Jameie B, Rajabi H. [Effect of endurance a nd high intensity interval swimming training on cardiac structure and Hand2 expression of Rats]. SSUJ 2017; 25:748-58.##Lu K, Wang L, Wang C, Yang Y, Hu D, Ding R. Effects of high intensity interval versus continuous moderate intensity aerobic exercise on apoptosis, oxidative stress and metabolism of the infarcted myocardium in a Rat model. Mole Med Rep 2015; 12:2374-82. doi.10.4103/ jrms.JRMS_292_18##Fathi M, Gharakhanlou R. [Effect of Endurance training on Hand2 gene expression in left ventricle of male Rats]. Sport Physiol 2015; 7: 57-68. (Persian)##Shioi T, Kang PM, Douglas PS, Hampe J, Yballe CM, Lawitts J. The conserved phosphoinositide 3‐kinase pathway determ-ines heart size in Mice. EMBO J2000; 19:2537-48. doi.10.1093/emboj/ 19.11.2537##Huenges K, Pokorny S, Berndt R, Cremer J, Lutter G. Transesophageal echocardiography in swine establishment of a baseline. Ult Med Biol2017; 43:974-80. doi.10.1016/j.ultrasmedbio.2016.12.011##Hoydal M, Wisloff U, Kemi OJ, Ellin-gsen O. Running speed and maximal oxy-gen uptake in rats and Mice practical imp-lications for exercise training. European J Cardiovas Preve Rehabil2007; 4:753-60. doi.10.1097/HJR.0b013e3281eacef1##Wisloff U, Loennechen JP, Currie S, Smith GL, Ellingsen O. Aerobic exercise reduces cardiomyocyte hypertrophy and increases contractility Ca2+ sensitivity and SERCA-2 in rat after myocardial infarction. Cardiovas Res2002;54: 162-74.doi.10. 1016/s0008-6363(01)00565-x##Sun Y, Wang J, Qiu XB, Yuan F, Li RG, Xu YJ, et al. A HAND2 loss of function mutation causes familial ventricular septal defect and pulmonary stenosis. Gen Genom Genet 2016; 6:987-92. doi.10.1534/g3. 115.026518##O'Neill B, Kim J, Wende AR, Theobald HA, Tuinei J, Buchanan J, Guo A, Zaha VG, Davis DK, Schell JC, Boudina S. A conserved role for phosphatidylinositol 3-kinase but not Akt signaling in mitochon-drial adaptations that accompany physiol-ogical cardiac hypertrophy. Cell Metab 2007; 6:294-306. doi. 10.1016/ j.cmet. 2007.09.001##Owen K, Pretorius L, McMullen JR. The protective effects of exercise and phosphor-inositide 3-kinase p110α in the failing heart. Clin Sci2009; 116:365-75. doi.10. 1042/CS20080183## ##

اثربخشی آموزش انعطاف ‌پذیری روان‌ شناختی مبتنی بر درمان پذیرش و تعهد بر فرسودگی عاطفی و کار هیجانی در پرستاران شاغل در بیمارستان‌ های شهر اهواز Effectiveness of Psychological Flexibility Training based on Acceptance and Commitment Therapy on Emotional Burn Out and Emotional Labor among Nurses Working at Hospitals in Ahvaz, Iran 1 1 مقدمه: هدف پژوهش حاضر بررسی اثربخشی آموزش انعطاف ­پذیری روان­ شناختی مبتنی بر درمان پذیرش و تعهد بر فرسودگی عاطفی و کار هیجانی در پرستاران  شاغل در بیمارستان ­های شهر اهواز بود. مواد و روش‌ ها: طرح پژوهش حاضر نیمه آزمایشی و از نوع پیش ‌آزمون-پس ‌آزمون با گروه کنترل بود. جامعه آماری پژوهش حاضر را کلیه پرستاران شاغل در بیمارستان‌ های شهر اهواز در سال 1397 تشکیل می ‌دهند. نمونه پژوهش به روش نمونه ­گیری هدفمند انتخاب شد؛ تعداد 40 نفر از پرستاران با در نظر گرفتن معیارهای ورود به مطالعه انتخاب شدند و به صورت تصادفی به یک گروه آزمایش و یک گروه کنترل گـــمارده شـــدند. آزمودنی­ های هر دو گروه قبل از شروع مداخله و پس از آن به پرسش نامه­ فرسودگی شغلی مسلش و مقیاس کار هیجانی دیفندورف و همکاران پاسخ دادند. در مورد گروه آزمایش مداخله درمانی شامل 3 جلسه آموزش انعطاف پذیری روان شناختی مبتنی بر درمان پذیرش و تعهد اجرا گردید، آزمودنی ­های گروه کنترل نیز در انتظار مداخله قرار گرفتند. داده ­ها با استفاده از آزمون تحلیل کوواریانس چندمتغیره مورد تجزیه و تحلیل قرار گرفت. یافته ‌های پژوهش: نتایج تجزیه و تحلیل داده ­ها نشان داد که بین دو گروه از لحاظ فرسودگی عاطفی(P=0.001, F=223.014) و کار هیجانی(P=0.001, F=273.731) تفاوت معنی ­داری وجود دارد. بحث و نتیجه ­گیری: بر مبنای یافته ­ها، می ­توان بیان داشت که آموزش انعطاف‌ پذیری روان ‌شناختی مبتنی بر درمان پذیرش و تعهد می­ تواند برای کاهش فرسودگی عاطفی و کار هیجانی در پرستاران مورد استفاده قرار گیرد. 2 Introduction: This study aimed to investigate the effectiveness of psychological flexibility training based on acceptance and commitment therapy on emotional burnout and emotional labor among nurses working at hospitals in Ahvaz, Iran.   Materials & Methods: This semi-experimental was conducted based on a pretest-posttest design and a control group. The study population included all nurses working at hospitals in Ahvaz, Iran, during 2019. In total, 40 nurses were selected using the purposeful sampling method based on the inclusion criteria and were randomly assigned to experimental and control groups. The participants in both groups were requested to respond to the Maslach burnout inventory and the Diefendorff et al. emotional labor scale before and after the intervention. The experimental group participated in three sessions of psychological flexibility training based on acceptance and commitment therapy. On the other hand, the control group awaited for the intervention. The data were analyzed using a multivariate analysis of covariance. Ethics code: EE/97.24.3.17688/SCU.AC.IR   Findings: The results of the data analysis showed a significant difference between the two groups in terms of emotional burn out (F=223.014, P=0.001) and emotional labor (F=273.731, P=0.001).   Discussions & Conclusions: Based on the findings, it can be stated that psychological flexibility training based on acceptance and commitment therapy can be used to reduce emotional burnout and emotional labor among nurses. 90 99 2020/05/192019/12/182019/09/252020/02/52020/01/142019/11/102019/09/152019/11/32019/01/5 1397/10/15 2020/09/162020/05/262020/04/282020/07/122020/02/12020/02/122020/04/142020/04/192019/02/6 1397/11/17 ساره میرشکار Sareh Mirshekar گروه روان شناسی، دانشکده علوم تربیتی و روان شناسی، دانشگاه شهید چمران اهواز، اهواز، ایران ایران sarehmirshekar@gmail.com سید اسماعیل هاشمی Seyed Esmaeil Hashemi گروه روان شناسی، دانشکده علوم تربیتی و روان شناسی، دانشگاه شهید چمران اهواز، اهواز، ایران ایران esmaeil12140@yahoo.com مهناز مهرابی زاده هنرمند Mahnaz Mehrabizade Honarmand گروه روان شناسی، دانشکده علوم تربیتی و روان شناسی، دانشگاه شهید چمران اهواز، اهواز، ایران ایران m.merabizadeeh@yahoo.com نسرین ارشدی Nasrin Arshadi گروه روان شناسی، دانشکده علوم تربیتی و روان شناسی، دانشگاه شهید چمران اهواز، اهواز، ایران ایران arshaadinasrin@gmail.com Acceptance and commitment therapy Emotional exhaustion Emotional labor Psychological flexibility انعطاف ‌پذیری روان‌ شناختی درمان پذیرش و تعهد فرسودگی عاطفی کار هیجانی Massoudi R, Aetemadifar S, Afzali S, Khayri F, Hassanpourdehkordi A. [The influential factors on burnout among nurses working in private hospitals in Tehran]. IJNR 2008:3: 47-58. (Persian)##Broom A, Kirby E, Good P, Wootton J, Yates P, Hardy J. Negotiating futility managing emotions nursing the transition to palliative care. Qual Health Res 2015;25:299-309. doi. 10.1177/1049732314553123.##Lundstrom T, Pugliese G, Bartley J, Cox J, Guither C. Organizational and environmental factors that affect worker health and safety and patient outcomes. Am J Infect Control 2002;30:93-106.##Maslach C, Schaufeli WB, Leiter MP. Job burnout. Annu Rev Psychol 2001;52:397-422. doi. 10.1146/annurev.psych.52.1.397.##Mathisen GE, Bergh LIV. Action errors and rule violations at offshore oil rigs the role of engagement emotional exhaustion and health complaints. Saf Sci 2016;85: 130-8. doi. 10.1016/j.ssci.2016.01.008##Chou HY, Hecker R, Martin A. Predicting nurses well‐being from job demands and resources: A cross‐sectional study of emotional labour. J Nurs Manage 2012;20:502-11. doi. 10.1111/j.1365-2834.2011.01305.##Hochschild AR. The managed heart the commercialization of human feeling. 1 th ed. Perface Berkeley Uni California Publication. 2012;111-9. doi.10.1002/pam.4050030365##Lee YH, Woo B. Emotional Intelligence emotional labor, and emotional exhaustion among korean fitness employees. J Glob Sport Manage 2017:2: 65-78. doi. 10.1080/24704067.2017.1283528##Yagil D, Medlerliraz H. Personally committed to emotional labor: surface acting emotional exhaustion and performance among service employees with a strong need to belong. J Occup Health Psychol 2017;22:481-91. doi.10.1037/ocp0000049.##Han SS, Han JW, Kim YH. Effect of nurse's emotional labor on customer orientation and service delivery the mediating effects of work engagement and burnout. Saf Health Work 2018; 9: 441-6. doi.10.1016/j.shaw.2017.12.001##Khaghanizade M, Siratinir M, Abdi F, Kaviani H. Assessing of mental health level of employed nurses in educational hospitals affiliated to Tehran medical sciences University. JFMH 2006: 8: 141-8.##Abdimasooleh F, Kaviani H, Khaghanizde M, Momeniaraghi A. The relationship between burnout and mental health among nurses. Tehran Uni Med J 2007:65: 65-75.##Duarte J, Pintogouveia J. Mindfulness self-compassion and psychological flexibility mediate effects of a mindfulness based intervention in a sample of oncology nurses. J Cont Behave Sci 2017:6:125 -33. doi.10.1016/j.jcbs.2017.03.002##Bond FW, Flaxman PE, Veldhoven MJPM, Biron M. The impact of psychological flexibility and acceptance and commitment therapy on health and productivity at work. Cont Occup Health Psychol Glob Res Pract Wiley 2010;1: 296-313. doi.10.1002/9780470661550.##Bond FW, Bunce D. The role of acceptance and job control in mental health, job satisfaction, and work performance. J Appl Psychol 2003; 88:1057-67. doi.10.1037/0021-9010.88.6.1057.##Obrien WH, Singh RS, Horan K, Moeller MT, Wasson R, Jex SM. Group based acceptance and commitment therapy for nurses and nurse aides working in long term care residential setting. J Altern Comple Med 2019; 25: 753-61. doi.10.1089/acm.2019.0087.##Fatehidehaghani F, Badami R. [The impact of acceptance and commitment based therapy on job stress, metacognitive beliefs attention and shooting performance among military personnel]. J Mil Psychol 2017; 8:19-28. (Persian)##Bahreinian S, khanjani S, Masjediarani A. [The efficacy of group acceptance and commitment therapy based training on burnout in nurses]. J Police Med 2016; 5 :143-52. (Persian)##Robins TG, Roberts RM, Sarris A. Burnout and engagement in health profession students the relationships between study demands study resources and personal resources. Australas J Organ Psychol 2015;8: 1-13. doi.10.1017/orp.2014.7.##Onwezen MC, Veldhoven MJPM, Biron M. The role of psychological flexibility in the demands exhaustion performance relationship. Eur J Work Org Psychol 2014; 23:163-76. doi.10.1080/1359432X.2012.742242.##Biron M, Veldhoven, M. Emotional labour in service work psychological flexibility and emotion regulation. HR 2012;65: 1259-82. doi.10.1177/0018726712447832.##Arshadi N, Neisi A, Esmaeili I. [The mediating role of work motivation in the relationship between emotional exhaustion and job performance based on conservation of resources model]. IJBS 2014;7: 327-45. (Persian)##Diefendorff JM, Croyle MH, Gosserand RH. The dimensionality and antecedents of emotional labor strategies. J Vocat Behave 2005:66, 339-59. doi.10.1016/j.jvb.2004.02.001.##Keyvanara M, Naemesfahani M, Bahrami S, Karimi S, Azizzadeh M. An Investigation of the relationship between emotional labor and job satisfaction among the executives and nursing managers of the teaching hospitals affiliated to Isfahan University of medical sciences. JHC 2015; 1 :47-54. (Persian)##Flaxman PE, Bond FW, Livheim F. The mindful and effective employee an acceptance and commitment therapy training manual for improving well‐being and performance. Oakland CA New Harb 2013; 2:153-7.##Khamisa N, Peltzer K, Oldenburg B. Burnout in relation to specific contributing factors and health outcomes among nurses a systematic review. Int J Environ Res Publ Health 2013; 10:2214-40. doi.10.3390/ijerph10062214.##Mulki JP, Jaramillo F, Locander WB. Emotional exhaustion and organizational deviance can the right job and a leader's style make a difference? J Bus Res 2006; 59:1222-30. doi. 10.1016/j.jbusres.2006.09.001.##Hayes SC, Bissett R, Roget N, Padilla M, Kohlenberg BS, Fisher G, et al. The impact of acceptance and commitment training and multicultural training on the stigmatizing attitudes and professional burnout of substance abuse counselors. Behave Ther 2004; 35:821 -35. doi. 10.1016/S0005-7894(04)80022-4##Hayes SC, Luoma JB, Bond FW, Masuda A, Lillis J. Acceptance and commitment theory model processes and outcomes. Behave Res Ther 2006;44:1-25. doi.10.1016/j.brat.2005.06.006.##Martinez D, Totterdell P, Alcover CM, Holman D. Emotional labor and emotional exhaustion: interpersonal and intrapersonal mechanisms. Work Stress 2007; 21: 30-47. doi.org/10.1080/02678370701234274##Massoudi R, Aetemadifar S, Afzali S, Khayri F, Hassanpourdehkordi A. [The influential factors on burnout among nurses working in private hospitals in Tehran]. IJNR 2008:3: 47-58. (Persian)##Broom A, Kirby E, Good P, Wootton J, Yates P, Hardy J. Negotiating futility managing emotions nursing the transition to palliative care. Qual Health Res 2015;25:299-309. doi. 10.1177/1049732314553123.##Lundstrom T, Pugliese G, Bartley J, Cox J, Guither C. Organizational and environmental factors that affect worker health and safety and patient outcomes. Am J Infect Control 2002;30:93-106.##Maslach C, Schaufeli WB, Leiter MP. Job burnout. Annu Rev Psychol 2001;52:397-422. doi. 10.1146/annurev.psych.52.1.397.##Mathisen GE, Bergh LIV. Action errors and rule violations at offshore oil rigs the role of engagement emotional exhaustion and health complaints. Saf Sci 2016;85: 130-8. doi. 10.1016/j.ssci.2016.01.008##Chou HY, Hecker R, Martin A. Predicting nurses well‐being from job demands and resources: A cross‐sectional study of emotional labour. J Nurs Manage 2012;20:502-11. doi. 10.1111/j.1365-2834.2011.01305.##Hochschild AR. The managed heart the commercialization of human feeling. 1 th ed. Perface Berkeley Uni California Publication. 2012;111-9. doi.10.1002/pam.4050030365##Lee YH, Woo B. Emotional Intelligence emotional labor, and emotional exhaustion among korean fitness employees. J Glob Sport Manage 2017:2: 65-78. doi. 10.1080/24704067.2017.1283528##Yagil D, Medlerliraz H. Personally committed to emotional labor: surface acting emotional exhaustion and performance among service employees with a strong need to belong. J Occup Health Psychol 2017;22:481-91. doi.10.1037/ocp0000049.##Han SS, Han JW, Kim YH. Effect of nurse's emotional labor on customer orientation and service delivery the mediating effects of work engagement and burnout. Saf Health Work 2018; 9: 441-6. doi.10.1016/j.shaw.2017.12.001##Khaghanizade M, Siratinir M, Abdi F, Kaviani H. Assessing of mental health level of employed nurses in educational hospitals affiliated to Tehran medical sciences University. JFMH 2006: 8: 141-8.##Abdimasooleh F, Kaviani H, Khaghanizde M, Momeniaraghi A. The relationship between burnout and mental health among nurses. Tehran Uni Med J 2007:65: 65-75.##Duarte J, Pintogouveia J. Mindfulness self-compassion and psychological flexibility mediate effects of a mindfulness based intervention in a sample of oncology nurses. J Cont Behave Sci 2017:6:125 -33. doi.10.1016/j.jcbs.2017.03.002##Bond FW, Flaxman PE, Veldhoven MJPM, Biron M. The impact of psychological flexibility and acceptance and commitment therapy on health and productivity at work. Cont Occup Health Psychol Glob Res Pract Wiley 2010;1: 296-313. doi.10.1002/9780470661550.##Bond FW, Bunce D. The role of acceptance and job control in mental health, job satisfaction, and work performance. J Appl Psychol 2003; 88:1057-67. doi.10.1037/0021-9010.88.6.1057.##Obrien WH, Singh RS, Horan K, Moeller MT, Wasson R, Jex SM. Group based acceptance and commitment therapy for nurses and nurse aides working in long term care residential setting. J Altern Comple Med 2019; 25: 753-61. doi.10.1089/acm.2019.0087.##Fatehidehaghani F, Badami R. [The impact of acceptance and commitment based therapy on job stress, metacognitive beliefs attention and shooting performance among military personnel]. J Mil Psychol 2017; 8:19-28. (Persian)##Bahreinian S, khanjani S, Masjediarani A. [The efficacy of group acceptance and commitment therapy based training on burnout in nurses]. J Police Med 2016; 5 :143-52. (Persian)##Robins TG, Roberts RM, Sarris A. Burnout and engagement in health profession students the relationships between study demands study resources and personal resources. Australas J Organ Psychol 2015;8: 1-13. doi.10.1017/orp.2014.7.##Onwezen MC, Veldhoven MJPM, Biron M. The role of psychological flexibility in the demands exhaustion performance relationship. Eur J Work Org Psychol 2014; 23:163-76. doi.10.1080/1359432X.2012.742242.##Biron M, Veldhoven, M. Emotional labour in service work psychological flexibility and emotion regulation. HR 2012;65: 1259-82. doi.10.1177/0018726712447832.##Arshadi N, Neisi A, Esmaeili I. [The mediating role of work motivation in the relationship between emotional exhaustion and job performance based on conservation of resources model]. IJBS 2014;7: 327-45. (Persian)##Diefendorff JM, Croyle MH, Gosserand RH. The dimensionality and antecedents of emotional labor strategies. J Vocat Behave 2005:66, 339-59. doi.10.1016/j.jvb.2004.02.001.##Keyvanara M, Naemesfahani M, Bahrami S, Karimi S, Azizzadeh M. An Investigation of the relationship between emotional labor and job satisfaction among the executives and nursing managers of the teaching hospitals affiliated to Isfahan University of medical sciences. JHC 2015; 1 :47-54. (Persian)##Flaxman PE, Bond FW, Livheim F. The mindful and effective employee an acceptance and commitment therapy training manual for improving well‐being and performance. Oakland CA New Harb 2013; 2:153-7.##Khamisa N, Peltzer K, Oldenburg B. Burnout in relation to specific contributing factors and health outcomes among nurses a systematic review. Int J Environ Res Publ Health 2013; 10:2214-40. doi.10.3390/ijerph10062214.##Mulki JP, Jaramillo F, Locander WB. Emotional exhaustion and organizational deviance can the right job and a leader's style make a difference? J Bus Res 2006; 59:1222-30. doi. 10.1016/j.jbusres.2006.09.001.##Hayes SC, Bissett R, Roget N, Padilla M, Kohlenberg BS, Fisher G, et al. The impact of acceptance and commitment training and multicultural training on the stigmatizing attitudes and professional burnout of substance abuse counselors. Behave Ther 2004; 35:821 -35. doi. 10.1016/S0005-7894(04)80022-4##Hayes SC, Luoma JB, Bond FW, Masuda A, Lillis J. Acceptance and commitment theory model processes and outcomes. Behave Res Ther 2006;44:1-25. doi.10.1016/j.brat.2005.06.006.##Martinez D, Totterdell P, Alcover CM, Holman D. Emotional labor and emotional exhaustion: interpersonal and intrapersonal mechanisms. Work Stress 2007; 21: 30-47. doi.org/10.1080/02678370701234274## ##

مطالعه‌ استریولوژیک اثر حفاظتی آلفا لیپوئیک اسید بر بافت کلیه به دنبال سمیت ایجاد شده با نانوذرات نقره در موش NMRI Stereological Study of the Protective Effect of Alpha-Lipoic Acid on Kidney Tissue following Toxicity with Silver Nanoparticles in NMRI Mice 1 1 مقدمه: امروزه با پیش رفت تکنولوژی و با استفاده از نانوذرات نقره(AgNPs) در محصولات مختلف نگرانی ‌هایی جدی در مورد استفاده از این ماده مطرح شده است. این مطالعه به منظور تعیین اثر آلفا لیپوئیک اسید(ALA) به عنوان یک آنتی اکسیدان قوی در برابر سمیت ناشی از(AgNPs) بر بافت کلیه موش ‌هایNMRI  انجام شد. مواد و روش­ ها: در این تحقیق 24 سر موش نر بالغ NMRI با میانگین وزنی 2±36 گرم به­ طور تصادفی به 4 گروه: کنترل، (AgNPs) (Kg/day/ mg500)، (ALA)(Kg/day/ mg100) و (AgNPs) به ­همراه(ALA) تقسیم و از طریق دهانی به مدت 35 روز تیمار شدند. در پایان، با تشریح موش ‌ها، کلیه چپ آن ‌ها خارج، فیکس، قالب‌ گیری، برش گیری و پاساژ بافتی انجام شد و با روش هماتوکسیلین-ائوزین رنگ‌ آمیزی گردید. سپس پارامترهای بیوشیمیایی و استریولوژیک کلیه مانند محاسبه حجم اجزای مختلف آن اندازه گیری شد. داده ­ها با نرم افزار  SPSSبررسی و تحلیل شدند. یافته ‌های پژوهش: در این پژوهش افزایش معنی داری در میزان میانگین حجم جسمک کلیوی P<0.005، گلومرول P<0.001، تافت P<0.001، غشای کپسول بومن P<0.001 و کاهش معنی داری در میانگین حجم کل فضای کپسول بومن P<0.001، حجم لومن پروکسیمال توبول P<0.05 در گروه(AgNPs) نسبت به گروه کنترل مشاهده شد. میزان اوره و مالون دی آلدئید در گروه(AgNPs) نسبت به کنترل افزایش P<0.001 و میزان ظرفیت آنتی اکسیدانی تام کاهش معنی دار P<0.001 از خود نشان داد. بحث و نتیجه گیری: ALA در بهبود آسیب کلیوی ناشی از نانوذرات نقره نقش حفاظتی دارد. 2 Introduction: Today, with the advancements in technology and the use of silver nanoparticles (AgNPs)in various products, serious concerns have been raised about the use of this substance. This study aimed to determine the effect of Alpha Lipoic Acid(ALA) as a potent antioxidant against the toxicity of AgNPs on kidney tissue of NMRI mice.   Materials & Methods: In this experimental study, 24 adult male NMRI mice with a mean weight of 36±2 g were randomly allocated into four groups of control, AgNPs (500 mg/kg/day), ALA (100 mg/kg/day), and AgNPs+ALA. Subsequently, they were treated orally for 35 days and sacrificed. The left kidney was taken out, fixed, sectioned, processed, and stained using the hematoxylin-eosin method. Following that, the biochemical and stereological parameters of the kidney, such as the volume calculation of its various components were measured in this study. The data were analyzed in SPSS software (version 16). Ethics code: P/2/97s3113     Findings: In this study, there was a significant increase in the mean volume of the renal corpuscle (P<0.005), glomerulus (P<0.001), Taft (P<0.001), and Bowman capsule membrane (P<0.001); however, a significant decrease was observed in the mean total volume of Bowman capsule space (P<0.001) and proximal tubule lumen volume (P<0.05) in the AgNPs group, compared to the control group. The level of urea and malondialdehyde (P<0.001) was increased in the AgNPs group, compared to the control group.  In addition, total antioxidant capacity (P<0.001) showed a significant decrease.   Discussions & Conclusions: The ALA has a protective role in ameliorating kidney damage caused by silver nanoparticles. 100 112 2020/05/192019/12/182019/09/252020/02/52020/01/142019/11/102019/09/152019/11/32019/01/52019/12/18 1398/9/27 2020/09/162020/05/262020/04/282020/07/122020/02/12020/02/122020/04/142020/04/192019/02/62020/06/22 1399/4/2 سیدمحمدعلی شریعت زاده Seyed Mohammad Ali Shariatzadeh گروه زیست شناسی، دانشکده علوم، دانشگاه اراک، اراک، ایران ایران s-shariatzadeh@araku.ac.ir مرتضی گودرزی Morteza Godarzi گروه زیست شناسی، دانشکده علوم، دانشگاه اراک، اراک، ایران ایران Alpha lipoic acid Kidney NMRI Mice Silver nanoparticles Stereology نانوذرات نقره آلفا لیپوئیک اسید کلیه استریولوژی موش NMRI Mody VV, Siwale R, Singh A, Mody HR. Introduction to metallic nanoparticles. 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Cytotoxic and genotoxic effects of silver nanoparticles in testicular cells. Toxicology2012; 291:65-72. doi. 10.1016/j.tox.2011.10.022##Prabhu S, Poulose EK. Silver nanoparticles mechanism of antimicrobial action synthesis medical applications and toxicity effects. Int Nano let 2012; 2:32. doi.10.1186/2228-5326-2-32##Kimura H, Sawada T, Oshima S, Kozawa K, Ishioka T, Kato M. Toxicity and roles of reactive oxygen species. Curr Drug Targ Inflam Allerg2005; 4: 489-95.doi.10.2174/1568010054526287##Akilesh S. Normal kidney function and structure. 1 th ed. Uni Washington Seat USA .2014; P.2716-33. doi.10.1016/B978-0-12-386456-7.05402-2##Heidari Z, Mahmoudzadehsagheb HR, Dezfoulian AR, Barbarestani M, Noori SMH. [A stereological analysis of renal glomeruli following chronic lead intoxication in Rat during a continuous period of 8 weeks]. Acta Med Iranica 2002; 40: 73-8. (Persian)##Forbes JM, Cooper ME, Oldfield MD, Thomas MC. Role of advanced glycation end products in diabetic nephropathy. 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