تاثیر تمرین مقاومتی بر محتوای پروتئین‌های مرتبط با استرس شبکه آندوپلاسمی (PERK و NRF2) در بطن چپ موش‌های سفید بزرگ آزمایشگاهی مبتلا به دیابت نوع 2

نوع مقاله : مقاله پژوهشی

نویسندگان

1 گروه علوم ورزشی، مؤسسه‌ی آموزش عالی آپادانا، شیراز، ایران

2 گروه آموزش تربیت بدنی، دانشگاه فرهنگیان، تهران، ایران

چکیده

مقدمه و هدف: در سال‌های اخیر تمرین مقاومتی به عنوان یک مداخله قوی برای بهبود سلامت عملکرد قلبی عروقی در افراد مبتلا به دیابت نوع 2 پیشنهاد شده است. از این رو، هدف از مطالعه حاضر تاثیر تمرین مقاومتی بر محتوای پروتئین‌های مرتبط با استرس شبکه آندوپلاسمی (PERK و NRF2) در بطن چپ موش‌های سفید بزرگ آزمایشگاهی مبتلا به دیابت نوع 2 است. 
 مواد و روش ها: در این مطالعه‌ی تجربی، 12 سر موش‌ سفید بزرگ ازمایشگاهی نر 2 ماهه از نژاد Sprague Dawley با میانگین وزن 20±280 گرم انتخاب شدند. دیابتی نوع 2 از طریق تزریق محلول‌های نیکوتین‌آمید و استرپتوزوتوسین القاء شد. موش‌های سفید بزرگ آزمایشگاهی به روش تصادفی به 2 گروه، تمرین مقاومتی دیابتی و کنترل دیابتی تقسیم شدند؛ تمرین مقاومتی شامل 8 هفته و هفته‌ای 3 جلسه بالارفتن از یک نردبان عمودی با شیب 85 درجه به طول یک متر با 26 پله و 2 سانتی‌متر فضای بین هر پله بود. برای سنجش محتوای پروتئین PERK و NRF2 از روش وسترن‌بلات استفاده شد. برای تجزیه‌ و تحلیل داده‌ها از آزمون‌ t-مستقل استفاده‏ شد و سطح معناداری 05/0P≤ بود.
نتایج: پس از 8 هفته تمرین مقاومتی محتوای پروتئین‌های PERK و NRF2 افزایش معنی‌داری را نسبت به گروه کنترل در بطن چپ قلب موش‌های سفید بزرگ آزمایشگاهی دیابتی نشان داد (به تریتب 01/0P= و 002/0P=).
نتیجه‌گیری: به نظر می‌رسد تمرین مقاومتی برای سلامت قلب آزمودنی‌های مبتلا به دیابت نوع 2 می‌تواند مفید باشد و در دستورالعمل توانبخشی متخصصان سلامتی قرار گیرد.

کلیدواژه‌ها

موضوعات


عنوان مقاله [English]

The effect of resistance training on the content of proteins associated with endoplasmic reticulum stress (PERK and NRF2) in the left ventricle of rats with type 2 diabetes

نویسندگان [English]

  • Fatemeh Solhdoust 1
  • Hamed Alizadeh Pahlavani 2
  • Mohammad Sherafati Moghadam 1
1 Department of Sport Sciences, Apadana Institute of Higher Education, Shiraz, Iran
2 Department of Physical Education, Farhangian University, Tehran, Iran
چکیده [English]

Background and Objective: In recent years, resistance training has been proposed as a powerful intervention to improve the health of cardiovascular function in people with type 2 diabetes. Therefore, the aim of this study is the effect of resistance training on the content of endoplasmic reticulum stress-related proteins (PERK and NRF2) in the left ventricle of rats with type 2 diabetes.
Materials and Methods: In this experimental study, 12 2-month-old male Sprague Dawley rats with an average weight of 280±20 grams were selected. Type 2 diabetes was induced by injecting nicotinamide and streptozotocin solutions. Rats were randomly divided into 2 groups, diabetic resistance training and diabetic control. Resistance training consisted of 8 weeks and 3 sessions per week of climbing a vertical ladder with an 85 degree slope, one meter long with 26 steps and 2 cm space between each step. Western blot method was used to measure PERK and NRF2 protein content. Independent t-test was used for data analysis and the significance level was P≤0.05.
Results: After 8 weeks of resistance training, the content of PERK and NRF2 proteins showed a significant increase compared to the control group in the left ventricle of the heart of diabetic rats (P=0.01 and P=0.002, respectively).
Conclusion: It seems that resistance training can be useful for the heart health of subjects with type 2 diabetes and can be included in the rehabilitation guidelines of health professionals.

کلیدواژه‌ها [English]

  • Resistance exercise
  • Endoplasmic reticulum
  • Left ventricle
  • PERK protein
  • NRF2 protein
  • Type 2 diabetes
  1. Wang Y, Lee D-c, Brellenthin AG, Sui X, Church TS, Lavie CJ, et al., editors. Association of muscular strength and incidence of type 2 diabetes. Mayo Clinic Proceedings; 2019: Elsevier.
  2. Nielsen R, Wiggers H, Thomsen HH, Bovin A, Refsgaard J, Abrahamsen J, et al. Effect of tighter glycemic control on cardiac function, exercise capacity, and muscle strength in heart failure patients with type 2 diabetes: a randomized study. BMJ Open Diabetes Research and Care. 2016;4(1):e000202.
  3. Pahlavani HA, Rajabi H, Nabiuni M, Motamedi P, Khaledi N. The effect of anaerobic exercise with melatonin consumption on the expression of Bax and Bcl-2 markers in rat myocardium after ischemic-reperfusion. Medical Journal of Tabriz University of Medical Sciences. 2019;41(3):68-77.
  4. De Jong KA, Czeczor JK, Sithara S, McEwen K, Lopaschuk GD, Appelbe A, et al. Obesity and type 2 diabetes have additive effects on left ventricular remodelling in normotensive patients-a cross sectional study. Cardiovascular diabetology. 2017;16:1-12.
  5. Pasini AMF, Stranieri C, Rigoni AM, De Marchi S, Peserico D, Mozzini C, et al. Physical exercise reduces cytotoxicity and up-regulates nrf2 and upr expression in circulating cells of peripheral artery disease patients: an hypoxic adaptation? Journal of Atherosclerosis and Thrombosis. 2018;25(9):808-20.
  6. Nouri H, Sheikholeslami-Vatani D, Moloudi MR. Changes in UPR-PERK pathway and muscle hypertrophy following resistance training and creatine supplementation in rats. Journal of physiology and biochemistry. 2021;77:331-9.
  7. Crilly MJ, Tryon LD, Erlich AT, Hood DA. The role of Nrf2 in skeletal muscle contractile and mitochondrial function. Journal of applied physiology. 2016;121(3):730-40.
  8. Zhang C, Li Y, Zhao J, Su K, He K, Da Y, et al. Endoplasmic reticulum stress regulates cardiomyocyte apoptosis in myocardial fibrosis development via PERK-mediated autophagy. Cardiovascular Toxicology. 2020;20:618-26.
  9. Zhang S, Tian W, Duan X, Zhang Q, Cao L, Liu C, et al. Melatonin attenuates diabetic cardiomyopathy by increasing autophagy of cardiomyocytes via regulation of VEGF-B/GRP78/PERK signaling pathway. Cardiovascular Diabetology. 2024;23(1):19.
  10. Sigal RJ, Kenny GP, Boulé NG, Wells GA, Prud'homme D, Fortier M, et al. Effects of aerobic training, resistance training, or both on glycemic control in type 2 diabetes: a randomized trial. Annals of internal medicine. 2007;147(6):357-69.
  11. Yuan Z, Xiao-Wei L, Juan W, Xiu-Juan L, Nian-Yun Z, Lei S. HIIT and MICT attenuate high-fat diet-induced hepatic lipid accumulation and ER stress via the PERK-ATF4-CHOP signaling pathway. Journal of physiology and biochemistry. 2022;78(3):641-52.
  12. Kasai S, Shimizu S, Tatara Y, Mimura J, Itoh K. Regulation of Nrf2 by mitochondrial reactive oxygen species in physiology and pathology. Biomolecules. 2020;10(2):320.
  13. Fathi R, Ebrahimi M, Khenar Sanami S. Effects of High Fat Diet and High Intensity Aerobic Training on Interleukin 6 Plasma Levels in Rats. Pathobiology Research. 2015;18(3):109-16.
  14. Safhi MM, Anwer T, Khan G, Siddiqui R, Sivakumar SM, Alam MF. The combination of canagliflozin and omega-3 fatty acid ameliorates insulin resistance and cardiac biomarkers via modulation of inflammatory cytokines in type 2 diabetic rats. The Korean Journal of Physiology & Pharmacology. 2018;22(5):493-501.
  15. Khalili A, Nekooeian AA, Khosravi MB. Oleuropein improves glucose tolerance and lipid profile in rats with simultaneous renovascular hypertension and type 2 diabetes. Journal of Asian Natural Products Research. 2017;19(10):1011-21.
  16. Thirupathi A, da Silva Pieri BL, Queiroz JAMP, Rodrigues MS, de Bem Silveira G, de Souza DR, et al. Strength training and aerobic exercise alter mitochondrial parameters in brown adipose tissue and equally reduce body adiposity in aged rats. Journal of physiology and biochemistry. 2019;75:101-8.
  17. Liu X, Kwak D, Lu Z, Xu X, Fassett J, Wang H, et al. Endoplasmic reticulum stress sensor protein kinase R–Like endoplasmic reticulum kinase (PERK) protects against pressure overload–induced heart failure and lung remodeling. Hypertension. 2014;64(4):738-44.
  18. Liu X, Kwak D, Lu Z, Xu X, Fassett J, Wang H, et al. Endoplasmic reticulum stress sensor PERK protects against pressure overload induced heart failure and lung remodeling. Hypertension. 2014;64(4):738.
  19. Mohammadpour-Asl S, Roshan-Milani B, Roshan-Milani S, Saboory E, Ghobadian B, Chodari L. Endoplasmic reticulum stress PERK-ATF4-CHOP pathway is involved in non-alcoholic fatty liver disease in type 1 diabetic rats: The rescue effect of treatment exercise and insulin-like growth factor I. Heliyon. 2024;10(5).
  20. Cheng F, Dun Y, Cheng J, Ripley-Gonzalez JW, Jiang W, You B, et al. Exercise activates autophagy and regulates endoplasmic reticulum stress in muscle of high-fat diet mice to alleviate insulin resistance. Biochemical and Biophysical Research Communications. 2022;601:45-51.
  21. Liu C-L, Li X, Hu G-L, Li R-J, He Y-Y, Zhong W, et al. Salubrinal protects against tunicamycin and hypoxia induced cardiomyocyte apoptosis via the PERK-eIF2α signaling pathway. Journal of geriatric cardiology: JGC. 2012;9(3):258.
  22. Lee J, Park J-H, Park S. Resistance exercise training inhibit endoplasmic reticulum stress in the aorta of Zucker diabetic fatty rats. 한국체육과학회지. 2018;27(6):1053-61.
  23. Smith RE, Tran K, Smith CC, McDonald M, Shejwalkar P, Hara K. The role of the Nrf2/ARE antioxidant system in preventing cardiovascular diseases. Diseases. 2016;4(4):34.
  24. Satta S, Mahmoud AM, Wilkinson FL, Yvonne Alexander M, White SJ. The role of Nrf2 in cardiovascular function and disease. Oxidative medicine and cellular longevity. 2017;2017(1):9237263.
  25. Tang J, Wu C, Xu Y, Yang B, Xi Y, Cai M, et al. Resistance training up-regulates Smyd1 expression and inhibits oxidative stress and endoplasmic reticulum stress in the heart of middle-aged mice. Free Radical Biology and Medicine. 2024;210:304-17.
  26. Shanmugam G, Challa AK, Devarajan A, Athmanathan B, Litovsky SH, Krishnamurthy P, et al. Exercise mediated Nrf2 signaling protects the myocardium from isoproterenol-induced pathological remodeling. Frontiers in cardiovascular medicine. 2019;6:68.
  27. Narasimhan M, Rajasekaran NS. Exercise, Nrf2 and antioxidant signaling in cardiac aging. Frontiers in physiology. 2016;7:241.
  28. Nadi Z, Abbasi Y, Jalali Mashayekhi F, Bayat M, Bayat P, Baazm M. Effect of Resistance and Endurance Trainings on Nrf2/Keap1 Signaling Pathway in Testicular Tissue of Type 2 Diabetic Rats. Journal of Mazandaran University of Medical Sciences. 2022;32(214):24-34.
  29. Noori S, Farajtabar Behrestaq S. Effects of Resistance Training with Intake of Aqueous Garlic Extract on the Expression of Nrf2 and PPARγ in the Liver of Diabetic Rats. Iranian Journal of Nutrition Sciences and Food Technology. 2024;19(1):29-37.
  30. Bahr AC, Scherer NB, de Gregório E, Kieling L, Türck P, Dal Lago P. Physical exercise and photobiomodulation increase nrf2 expression in the skeletal muscle of rats with heart failure and diabetes mellitus. Brazilian Journal of Physical Therapy. 2024;28:100599.
  31. Mohammad N, Matinhomaee H, Hosseini SA. Antioxidant effects of resistance training with pumpkin seed extract consumption in heart tissue of rats exposed to H2O2-induced oxidative damage. Zahedan Journal of Research in Medical Sciences. 2021;23(3).
  32. Powers S, Sollanek K, Wiggs M, Demirel H, Smuder A. Exercise-induced improvements in myocardial antioxidant capacity: the antioxidant players and cardioprotection. Free radical research. 2014;48(1):43-51.
  33. Azizbeigi K, Stannard SR, Atashak S, Haghighi MM. Antioxidant enzymes and oxidative stress adaptation to exercise training: Comparison of endurance, resistance, and concurrent training in untrained males. Journal of exercise science & fitness. 2014;12(1):1-6.
  34. Narasimhan M, Rajasekaran N-S. Cardiac Aging–Benefits of Exercise, Nrf2 Activation and Antioxidant Signaling. Exercise for Cardiovascular Disease Prevention and Treatment: From Molecular to Clinical, Part 1. 2017:231-55.
  35. Estébanez B, Visavadiya NP, Vargas JE, Rivera-Viloria M, Khamoui AV, de Paz JA, et al. Resistance training modulates reticulum endoplasmic stress, independent of oxidative and inflammatory responses, in elderly people. Antioxidants. 2022;11(11):2242.