ورزش و علوم زیست حرکتی

ورزش و علوم زیست حرکتی

تأثیر تمرین هوازی بر بیان ژن mir-195 در بافت قلب موش‌های صحرایی مبتلا به دیابت نوع دو

نوع مقاله : مقاله پژوهشی

نویسندگان
1 استادیار، گروه فیزیولوژی ورزشی، دانشکده تربیت بدنی و علوم ورزشی، دانشگاه تبریز، تبریز، ایران.
2 دانشجوی دکتری، گروه فیزیولوژی ورزشی، دانشکده تربیت بدنی و علوم ورزشی، دانشگاه تبریز، تبریز، ایران.
3 دانشیار بافت شناسی مقایسه‌ای، گروه علوم پایه، دانشکده دامپزشکی، دانشگاه تبریز، تبریز، ایران.
چکیده
مقدمه و هدف: در سال‌های اخیر رابطه بسیار نزدیکی بین miRNA و بیماری‌های دیابت و قلبی عروقی پیدا شده است. بنابراین، این تحقیق با هدف بررسی تاثیر هشت هفته تمرین هوازی بر بیان ژنmir-195 در بافت قلب موش‌های صحرایی مبتلا به دیابت نوع دو انجام شد.
مواد و روش­‌ها: برای این منظور، 18 سر موش صحرایی نر نژاد ویستار (با میانگین وزنی 240 گرم و میانگین سن 8 هفته‌ای) بصورت تصادفی به سه گروه 1) کنترل سالم، 2) کنترل دیابتی، و 3) تمرین دیابتی تقسیم شدند. برای القاء دیابت نوع دو، ابتدا یک رژیم­‌غذایی پرچرب (60 درصد) به مدت دو هفته و سپس تزریق استرپتوزوسین در حالت ناشتا صورت گرفت. پروتکل تمرین دویدن روی تردمیل پنج روز در هفته با رعایت اصل اضافه بار در هفته اول با سرعت 10-5 متر در دقیقه به مدت 10-15 دقیقه و در هفته هشتم با سرعت 18-24 متر در دقیقه به مدت 60 دقیقه به دست آمد. برای بررسی بیان ژن miR-195 از روش Real-time PCR استفاده شد. از آزمون‌­های تحلیل واریانس یک‌راهه و تعقیبی توکی، در سطح معنی­داری 0.05≥P استفاده شد.
یافته‌­ها: هشت هفته ابتلاء به T2DM منجر به افزایش معنی‌­دار در گلوکز و بیان ژن miR-195 شد (0.05≥P). با این حال هشت هفته تمرین هوازی منجر به کاهش معنی­‌دار در گلوکز و بیان ژن miR-195  نسبت به گروه کنترل دیابتی شد (0.05≥P).
نتیجه‌گیری: نتایج ما نشان داد که ورزش به ویژه تمرینات هوازی یک استراتژی مناسب برای کاهش miR-195 و بهبود عملکرد میوکارد در موش‌های دیابتی است.
کلیدواژه‌ها

موضوعات


عنوان مقاله English

The effect of aerobic training on the mir-195 gene expression in heart tissue of type 2 diabetic rats

نویسندگان English

Elaheh Piralaiy 1
Badrkhan Rashwan Ismael 2
Gholamreza Hamidian 3
1 Assistant Professor, Department of Exercise Physiology, Faculty of Physical Education and Sports Sciences, Tabriz University, Tabriz, Iran.
2 Ph.D Candidate, Department of Exercise Physiology, Faculty of Physical Education and Sports Sciences, Tabriz University, Tabriz, Iran.
3 3. Associate Professor in Comparative Histology, Department of Basic Sciences, Faculty of Veterinary Medicine, University of Tabriz, Tabriz, Iran.
چکیده English

Introduction and Purpose: In recent years, a strong association has been identified between miRNA and diseases such as diabetes and cardiovascular disorders. Therefore, this study aimed to investigate the effect of eight weeks of aerobic exercise on the expression of the mir-195 gene in the heart tissue of rats with type 2 diabetes.
Materials and methods: For this purpose, 18 male Wistar rats (average weight: 240 g, average age: 8 weeks) were randomly assigned to three groups: (1) healthy control, (2) diabetic control, and (3) diabetic exercise. To induce type 2 diabetes, the rats were first fed a high-fat diet (60%) for two weeks, followed by fasting streptozotocin injection. The treadmill running protocol was performed five days a week, following the principle of progressive overload. In the first week, the exercise was conducted at a speed of 5–10 m/min for 10–15 minutes, and by the eighth week, it was increased to 18–24 m/min for 60 minutes. Gene expression of miR-195 was assessed using real-time PCR. One-way ANOVA and Tukey’s post hoc test were used for statistical analysis at a significance level of P≤0.05.
Results: Eight weeks of T2DM led to a significant increase in glucose levels and miR-195 gene expression (P≤0.05). However, eight weeks of aerobic exercise significantly reduced glucose levels and miR-195 gene expression compared to the diabetic control group (P≤0.05).
Discussion and Conclusion: Our results suggest that exercise, particularly aerobic training, is an effective strategy for reducing miR-195 expression and improving myocardial function in diabetic rats.

کلیدواژه‌ها English

Aerobic training
mir-195 gene
Heart tissue
Rats
Type 2 diabetes
  1. Cho NH, Shaw JE, Karuranga S, Huang Y, da Rocha Fernandes JD, Ohlrogge AW, et al. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018;138. doi: 10.1016/j.diabres.2018.02.023.
  2. Caria ACI, Nonaka CKV, Pereira CS, Soares MBP, Macambira SG, Souza BS de F. Exercise training-induced changes in microRNAs: Beneficial regulatory effects in hypertension, type 2 diabetes, and obesity. Vol. 19, International Journal of Molecular Sciences. doi: 10.3390/ijms19113608.
  3. Chandrasekera D, Katare R. Exosomal microRNAs in diabetic heart disease. Vol. 21, Cardiovascular Diabetology. 2022. doi: 10.1186/s12933-022-01544-2.
  4. Hayat SA, Patel B, Khattar RS, Malik RA. Diabetic cardiomyopathy: Mechanisms, diagnosis and treatment. Vol. 107, Clinical Science. 2004. doi: 10.1042/CS20040057.
  5. Lew JKS, Pearson JT, Saw E, Tsuchimochi H, Wei M, Ghosh N, et al. Exercise Regulates MicroRNAs to Preserve Coronary and Cardiac Function in the Diabetic Heart. Circ Res. 2020;127(11). doi: 10.1161/CIRCRESAHA.120.317604.
  6. Mahjoob G, Ahmadi Y, Fatima rajani H, khanbabaei N, Abolhasani S. Circulating microRNAs as predictive biomarkers of coronary artery diseases in type 2 diabetes patients. Vol. 36, Journal of Clinical Laboratory Analysis. 2022. doi:10.1002/jcla.24380.
  7. Fluitt MB, Mohit N, Gambhir KK, Nunlee-Bland G. To the Future: The Role of Exosome-Derived microRNAs as Markers, Mediators, and Therapies for Endothelial Dysfunction in Type 2 Diabetes Mellitus. Vol. 2022, Journal of Diabetes Research. 2022. doi: 10.1155/2022/5126968.
  8. Shen YH, Xie ZB, Yue AM, Wei QD, Zhao HF, Yin HD, et al. Expression level of microRNA-195 in the serum of patients with gastric cancer and its relationship with the clinicopathological staging of the cancer. Eur Rev Med Pharmacol Sci. 2016;20(7). doi: 10.18632/oncotarget.21919.
  9. Yu W, Liang X, Li X, Zhang Y, Sun Z, Liu Y, et al. MicroRNA-195: A review of its role in cancers. Vol. 11, OncoTargets and Therapy. 2018. doi: 10.2147/OTT.S183600.
  10. Guo R, Nair S. Role of microRNA in diabetic cardiomyopathy: From mechanism to intervention. Vol. 1863, Biochimica et Biophysica Acta - Molecular Basis of Disease. 2017. doi: 10.1016/j.bbadis.2017.03.013.
  11. Ghosh N, Katare R. Molecular mechanism of diabetic cardiomyopathy and modulation of microRNA function by synthetic oligonucleotides. Vol. 17, Cardiovascular Diabetology. 2018. doi: 10.1186/s12933-018-0684-1.
  12. Chen H, Untiveros GM, McKee LAK, Perez J, Li J, Antin PB, et al. Micro-RNA-195 and -451 regulate the LKB1/AMPK signaling axis by targeting MO25. PLoS One. 2012;7(7). doi: 10.1371/journal.pone.0041574.
  13. Porrello ER, Johnson BA, Aurora AB, Simpson E, Nam YJ, Matkovich SJ, et al. MiR-15 family regulates postnatal mitotic arrest of cardiomyocytes. Circ Res. 2011;109(6). doi: 10.1161/CIRCRESAHA.111.248880.
  14. Delfan M, Kordi MR, Ravasi AA, Safa M, Nasli Esfahani E, Rambod K. The Effect of High-Intensity Interval Training and Continuous Endurance Training on Gene Expression of mir-1 and IGF-1 in Cardiomyocyte of Diabetic Male Rats. Journal of Sport Biosciences. 2021 May 22, 13(1):11–23. doi: 10.22059/JSB.2021.118369.892. [In Persian].
  15. Khakdan S, Delfan M, Heydarpour Meymeh M, Kazerouni F, Ghaedi H, Shanaki M, et al. High-intensity interval training (HIIT) effectively enhances heart function via miR-195-dependent cardiomyopathy reduction in high-fat high-fructose diet-induced diabetic rats. Arch Physiol Biochem. 2020;126(3).doi: 10.1080/13813455.2018.1511599.
  16. Zheng D, Ma J, Yu Y, Li M, Ni R, Wang G, et al. Silencing of miR-195 reduces diabetic cardiomyopathy in C57BL/6 mice. Diabetologia. 2015;58(8). doi: 10.1007/s00125-015-3622-8.
  17. Ding H, Yao J, Xie H, Wang C, Chen J, Wei K, et al. MicroRNA-195-5p Downregulation Inhibits Endothelial Mesenchymal Transition and Myocardial Fibrosis in Diabetic Cardiomyopathy by Targeting Smad7 and Inhibiting Transforming Growth Factor Beta 1-Smads-Snail Pathway. Front Physiol. 2021;12. doi: 10.3389/fphys.2021.709123.
  18. Colberg SR, Sigal RJ, Yardley JE, Riddell MC, Dunstan DW, Dempsey PC, et al. Physical activity/exercise and diabetes: A position statement of the American Diabetes Association. Vol. 39, Diabetes Care. 2016. doi: 10.2337/dc16-1728.
  19. Maryam D, Mohammad Reza K, Asghar Ra, Majid S, Ansieh Na, Kamelia R. The effect of a period of intense intermittent training and continuous endurance on the expression of mir-1 and IGF 1 gene in cardiomyocytes of diabetic male rats. Vol. 13. Sports biological sciences (movement); 2021. p. 1–13. doi.org/10.22059/jsb.2021.118369.892. [In Persian].
  20. Kashef M, Salehpour M, Shahidi F, Nejatmand N. Comparing the Effect of Six Weeks of Aerobic and Resistance Training on Expression miR-195 in Male Rats with Diabetic Cardiomyopathy. Journal of Isfahan Medical School. 2023;40(704). doi 10.48305/jims.v40.i704.1128. [In Persian].
  21. Sasidharan SR, Joseph JA, Anandakumar S, Venkatesan V, Ariyattu Madhavan CN, Agarwal A. An experimental approach for selecting appropriate rodent diets for research studies on metabolic disorders. Biomed Res Int. 2013;2013. doi: 10.1155/2013/752870.
  22. Srinivasan K, Viswanad B, Asrat L, Kaul CL, Ramarao P. Combination of high-fat diet-fed and low-dose streptozotocin-treated rat: A model for type 2 diabetes and pharmacological screening. Pharmacol Res. 2005;52(4). doi: 10.1016/j.phrs.2005.05.004.
  23. Schwingshackl L, Missbach B, Dias S, König J, Hoffmann G. Impact of different training modalities on glycaemic control and blood lipids in patients with type 2 diabetes: A systematic review and network meta-analysis. Vol. 57, Diabetologia. 2014. doi: 10.1007/s00125-014-3303-z.
  24. Nakos I, Kadoglou NPE, Gkeka P, Tzallas AT, Giannakeas N, Tsalikakis DG, et al. Exercise training attenuates the development of cardiac autonomic dysfunction in diabetic rats. In Vivo (Brooklyn). 2018;32(6). doi: 10.21873/invivo.11396.
  25. Mehri K, Hamidian G, Babri S, Farajdokht F, Zavvari Oskuye Z. Exercise and insulin glargine administration in mothers with diabetes during pregnancy ameliorate function of testis in offspring: Consequences on apelin-13 and its receptor. Life Sci. 2024 Apr 1;342:122517. doi: 10.1016/J.LFS.2024.122517.
  26. Waring CD, Vicinanza C, Papalamprou A, Smith AJ, Purushothaman S, Goldspink DF, et al. The adult heart responds to increased workload with physiologic hypertrophy, cardiac stem cell activation, and new myocyte formation. Eur Heart J. 2014;35(39). doi: 10.1093/eurheartj/ehs338.
  27. Eimen M, Hosseinzadeh H. Animal modeles if diabetes. Journal of Diabetes and Metabolic Disorders. 2003: 2(0):33. Available from: https://jdmd.tums.ac.ir/index.php/jdmd/article/view/29. [In Persian].
  28. Amini ali, parto paria, Yousufvand namdar. The effect of induced diabetes and its treatment with zinc sulfate & vanadium on the reproductive system in rats. Studies in Medical Sciences. 2016: 27(6):476–85. Available from: http://umj.umsu.ac.ir/article-1-3271-en.html. [In Persian].
  29. Khakdan S, Delfan M, Heydarpour Meymeh M, Kazerouni F, Ghaedi H, Shanaki M, et al. High-intensity interval training (HIIT) effectively enhances heart function via miR-195-dependent cardiomyopathy reduction in high-fat high-fructose diet-induced diabetic rats. Arch Physiol Biochem. 2020;126(3). doi: 10.1080/13813455.2018.1511599.
  30. Wang H, Bei Y, Lu Y, Sun W, Liu Q, Wang Y, et al. Exercise prevents cardiac injury and improves mitochondrial biogenesis in advanced diabetic cardiomyopathy with PGC-1α and Akt activation. Cellular Physiology and Biochemistry. 2015;35(6). doi: 10.1159/000374021.
  31. Ramzany N, Gaeini A, Choobineh S, Kordi M, Hedayati M. Changes of RBP-4 and insulin resistance after 8 weeks of aerobic training in type 2 diabetic rats. Metabolism and Exercise. 2017 Jan 20: 5(2):89–98. Available from: https://jme.guilan.ac.ir/article_2065_en.html. [In Persian].
  32. Błaszczyk R, Petniak A, Bogucki J, Kocki J, Wysokiński A, Głowniak A. Association between Resistant Arterial Hypertension, Type 2 Diabetes, and Selected microRNAs. J Clin Med. 2024 Jan 18;13(2):542. doi: 10.3390/jcm13020542.
  33. Shrivastav D, Singh DD. Emerging roles of microRNAs as diagnostics and potential therapeutic interest in type 2 diabetes mellitus. World J Clin Cases. 2024;12(3). doi: 10.12998/wjcc.v12.i3.525.
  34. Margolis LM, Lessard SJ, Ezzyat Y, Fielding RA, Rivas DA. Circulating MicroRNA Are Predictive of Aging and Acute Adaptive Response to Resistance Exercise in Men. Journals of Gerontology - Series A Biological Sciences and Medical Sciences. 2017;72(10). doi: 10.1093/gerona/glw243.
  35. Rowlands DS, Page RA, Sukala WR, Giri M, Ghimbovschi SD, Hayat I, et al. Multi-Omic integrated networks connect DNA methylation and miRNA with skeletal muscle plasticity to chronic exercise in type 2 diabetic obesity. Physiol Genomics. 2014;46(20). doi: 10.1152/physiolgenomics.00024.2014.
  36. Papait R, Serio S, Condorelli G. Role of the epigenome in heart failure. Vol. 100, Physiological Reviews. 2020. doi: 10.1152/physrev.00037.2019.
  37. Dores H, Freitas A, Malhotra A, Mendes M, Sharma S. The hearts of competitive athletes: An up-to-date overview of exercise-induced cardiac adaptations. Vol. 34, Revista Portuguesa de Cardiologia. 2015. doi: 10.1016/j.repc.2014.07.010.
  38. Sulaiman M, Matta MJ, Sunderesan NR, Gupta MP, Periasamy M, Gupta M. Resveratrol, an activator of SIRT1, upregulates sarcoplasmic calcium ATPase and improves cardiac function in diabetic cardiomyopathy. Am J Physiol Heart Circ Physiol. 2010;298(3). doi: 10.1152/ajpheart.00418.2009.

Zhou F, Yang Y, Xing D. Bcl-2 and Bcl-xL play important roles in the crosstalk between autophagy and apoptosis. FEBS Journal. 2011;278(3). doi: 10.1111/j.1742-4658.2010.07965.x.

دوره 16، شماره 32
اسفند 1403
صفحه 39-49

  • تاریخ دریافت 12 خرداد 1403
  • تاریخ بازنگری 24 شهریور 1403
  • تاریخ پذیرش 07 مهر 1403