اثر تمرینات هوازی تداومی و تناوبی بر بیان ژن‌های p53 و Bax و ارتباط آن با استرس اکسیداتیو و مرگ برنامه‌ریزی‌شده سلولی در میوکارد رت‌های مبتلا به انفارکتوس

نوع مقاله : مقاله پژوهشی

نویسندگان

1 گروه علوم ورزشی، واحد نجف آباد، دانشگاه آزاد اسلامی، نجف آباد، ایران

2 گروه علوم ورزشی، واحد نجف آباد، دانشگاه آزاد اسلامی، نجف آباد، ایران. (نویسنده مسئول)

3 گروه علوم ورزشی ، دانشگاه اصفهان، اصفهان، ایران‌

چکیده

مقدمه: آنفارکتوس میوکارد (MI) یکی از عوامل اصلی مرگ‌ومیر قلبی‌عروقی در جهان است که باعث ایجاد استرس اکسیداتیو و مرگ برنامه‌ریزی‌شده سلولی در بافت قلب می‌شود. این مطالعه تأثیر تمرینات هوازی تداومی (MICT) و تناوبی با شدت بالا (HIIT) را بر بیان ژن‌های p53 و Bax و ارتباط آن‌ها با استرس اکسیداتیو و آپوپتوز در میوکارد موش‌های نر ویستار پس از MI بررسی کرد.
روش کار:  30 موش (سن 10 تا 12 هفته، وزن 275 ± 25 گرم) به پنج گروه تقسیم شدند: کنترل سالم (Ct)، کنترل جراحی (Sham)، MI بدون تمرین (OLAD)، MI با MICT و MI با HIIT.  انفارکتوس با بستن شریان نزولی قدامی چپ القا شد و با الکتروکاردیوگرافی و اکوکاردیوگرافی تأیید گردید. MICT شامل جلسات 50 دقیقه‌ای با شدت 50-60% VO₂max و HIIT شامل هفت بازه 4 دقیقه‌ای با شدت 85-90% VO₂max با ریکاوری فعال 3 دقیقه‌ای بود که 5 روز در هفته به مدت 8 هفته انجام شد.
نتایج: بیان ژن‌ها (p53، Bax) و نشانگرهای استرس اکسیداتیو (SOD، GPx، GSH/GSSG، TAC، 8-OHdG) با RT-PCR و ELISA ارزیابی شدند. MI به‌طور معناداری بیان 53p (1.8 برابر) و Bax  (0.65 نانوگرم/میلی‌گرم) را افزایش داد و همراه با افزایش آسیب اکسیداتیو (8-OHdG، NOX4، p66Shc)  و کاهش سطوح آنتی‌اکسیدانی (SOD، GSH/GSSG) بود. هر دو MICT و HIIT این تغییرات را کاهش دادند، با برتری HIIT در کاهش (p=0.047)  53p   و 8-OHdG. تحلیل‌های رگرسیون نشان داد که SOD، GSH/GSSG و 8-OHdG پیش‌بین‌های اصلی بیان ژن‌های آپوپتوتیک هستند.
نتیجه گیری: این یافته‌ها نشان می‌دهند که HIIT، بیش از MICT، با تعدیل استرس اکسیداتیو، آپوپتوز ناشی از MI را کاهش می‌دهد و پتانسیل بهینه‌سازی استراتژی‌های بازتوانی قلبی را دارد.

کلیدواژه‌ها

عنوان مقاله [English]

Effects of Continuous and High-Intensity Interval Aerobic Training on p53 and Bax Gene Expression and Their Association with Oxidative Stress and Programmed Cell Death in the Myocardium of Rats with Myocardial Infarction

نویسندگان [English]

  • Bahareh Mardani 1
  • Saeed Keshavarz 2
  • Hossein Mojtahedi 3
  • Leila Sarram i 1
1 Department of Sport Sciences, Na.C., Islamic Azad University, NajafAbad, Iran
2 Department of Sport Sciences, Na.C., Islamic Azad University, NajafAbad, Iran (Corresponding Author)
3 Department of Sport Sciences, University of Isfahan, Isfahan, Iran
چکیده [English]

Introduction: Myocardial infarction (MI) is a leading cause of cardiovascular mortality worldwide and is associated with increased oxidative stress and programmed cell death in cardiac tissue. The present study aimed to investigate the effects of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) on p53 and Bax gene expression, as well as their association with oxidative stress and apoptosis in the myocardium of male Wistar rats following MI.
 Methods: Thirty male Wistar rats (aged 10–12 weeks, weighing 275 ± 25 g) were randomly assigned to five groups: healthy control (Ct), sham-operated (Sham), MI without training (OLAD), MI + MICT, and MI + HIIT. Myocardial infarction was induced via ligation of the left anterior descending (LAD) coronary artery and confirmed by electrocardiography and echocardiography. The MICT protocol consisted of 50-minute sessions at 50–60% VO₂max, whereas the HIIT protocol included seven 4-minute intervals at 85–90% VO₂max interspersed with 3-minute active recovery periods. Training was performed five days per week for eight weeks. Gene expression levels (p53 and Bax) and oxidative stress markers (SOD, GPx, GSH/GSSG ratio, TAC, and 8-OHdG) were assessed using real-time PCR and ELISA.
Results: MI significantly increased p53 expression (1.8-fold) and Bax levels (0.65 ng/mg), accompanied by elevated oxidative damage markers (8-OHdG, NOX4, and p66Shc) and reduced antioxidant capacity (SOD and GSH/GSSG ratio). Both MICT and HIIT significantly attenuated these alterations; however, HIIT demonstrated greater efficacy in reducing p53 expression (p = 0.047) and 8-OHdG levels. Regression analysis indicated that SOD, GSH/GSSG ratio, and 8-OHdG were significant predictors of apoptotic gene expression.
Conclusion: These findings suggest that HIIT is more effective than MICT in attenuating MI-induced apoptosis through modulation of oxidative stress pathways and may serve as a promising strategy for optimizing cardiac rehabilitation interventions.

کلیدواژه‌ها [English]

  • Myocardial Infarction
  • Aerobic Exercise
  • P53
  • Bax
  • Oxidative Stress

مراجع

  1. Guo J, Huang Y, Pang L, Zhou Y, Yuan J, Zhou B, et al. Association of systemic inflammatory response index with ST segment elevation myocardial infarction and degree of coronary stenosis: a cross-sectional study. BMC Cardiovasc Disord. 2024;24(1):98.
  2. Papamichail A, Kourek C, Briasoulis A, Xanthopoulos A, Tsougos E, Farmakis D, et al. Targeting key inflammatory mechanisms underlying heart failure: a comprehensive review. Int J Mol Sci. 2023;25(1):510.
  3. Valenzuela PL, Ruilope LM, Santos-Lozano A, Wilhelm M, Kränkel N, Fiuza-Luces C, et al. Exercise benefits in cardiovascular diseases: from mechanisms to clinical implementation. Eur Heart J. 2023;44(21):1874-89.
  4. Shahidi F, Kashef M, Delfani Z. A review of exercise-based cardiac rehabilitation strategies in patients with myocardial infarction: focus on high-intensity interval training. Arak University of Medical Sciences Journal. 2021;24(6):778-791.
  5. Mongirdienė A, Skrodenis L, Varoneckaitė L, Mierkytė G, Gerulis J. Reactive oxygen species induced pathways in heart failure pathogenesis and potential therapeutic strategies. Biomedicines. 2022;10(3):602.
  6. Martens MD, Karch J, Gordon JW. The molecular mosaic of regulated cell death in the cardiovascular system. Biochim Biophys Acta Mol Basis Dis. 2022;1868(1):166297.
  7. Song P, Sun M, Liu C, Liu J, Lin P, Chen H, et al. Reactive oxygen species damage bovine endometrial epithelial cells via the cytochrome C-mPTP pathway. Antioxidants. 2023;12(12):2123.
  8. Cai S, Zhao M, Zhou B, Yoshii A, Bugg D, Villet O, et al. Mitochondrial dysfunction in macrophages promotes inflammation and suppresses repair after myocardial infarction. J Clin Invest. 2023;133(4).
  9. Jin W, Liu M, Zhang X, Zhang X. Comparison of aerobic exercise effects on oxidative stress and apoptosis in rats with myocardial infarction. Mol Med Rep. 2015;12(4):4949-55.
  10. Jiang, H. K., Wang, Y. H., Sun, L., He, X., Zhao, M., Feng, Z. H., ... & Zang, W. J. (2014). Aerobic interval training attenuates mitochondrial dysfunction in rats post-myocardial infarction: roles of mitochondrial network dynamics. International journal of molecular sciences, 15(4), 5304-5322.
  11. Xiang Q, Yi X, Zhu XH, Wei X, Jiang DS. Regulated cell death in myocardial ischemia–reperfusion injury. Trends Endocrinol Metab. 2024;35(3):219-34.
  12. Mendes RF, Sousa MS, Sampaio R, Silva MT. Comparative effects of continuous and interval aerobic training on cardiac function in chronic heart failure rats. Physiol Res. 2017;66(2):203-12.
  13. Rostami N, Afroondeh R, Seifi Asgari Shahr F, Pourrahim Ghorghchi A. Effect of moderate-intensity interval training on the expression of necroptosis-related genes in cardiac tissue of male mice with myocardial infarction model. Journal of Shahid Sadoughi University of Medical Sciences. 2024;32(8):8173-8186.
  14. Seo DY, Bae JH, Li X, Han J. Exercise training and cardiovascular health: Mechanisms, benefits, and therapeutic implications in cardiovascular disease. CardioMetab Syndr J. 2023;3(2):123-34.
  15. Kim JS, Cho MK, Lee HJ. The effects of intermittent and continuous exercise on oxidative stress and cardiac function in rats with heart failure. J Sports Rehabil. 2021;17(1):19-26.
  16. Ahmadi R, Fathi M, Rahmati M. Effect of high-intensity interval training and crocin consumption on serum markers of cardiac tissue toxicity induced by doxorubicin injection in male Wistar rats. Complementary Medicine Journal. 2022;12(2):136-147.
  17. Ebrahimi M, Asgharpoor H, Farzangi P, Rezaei Shirazi R. Effect of two types of training (continuous and interval) and atorvastatin on PP2Ac and GSK-3β gene expression in cardiac tissue of diabetic model rats. Journal of Plasma and Biomarkers. 2023;16(3):86-98.
  18. Bennett E, Devan H, Hale L, Gray E. Evaluation of the quality and self-management-related content of websites promoting physical activity engagement after myocardial infarction or cardiac surgery: A scoping review. Heart Lung. 2025;69:94-110.
  19. Charan J, Biswas T. How to calculate sample size for different study designs in medical research? Indian J Psychol Med. 2013;35(2):121-6.
  20. Høydal MA, Wisløff U, Kemi OJ, Ellingsen Ø. Running speed and maximal oxygen uptake in rats and mice: practical implications for exercise training. Eur J Prev Cardiol. 2007;14(6):753-60.
  21. Khalafi M, Mohebbi H, Symonds ME, Karimi P, Akbari A, Tabari E, et al. The impact of moderate-intensity continuous or high-intensity interval training on adipogenesis and browning of subcutaneous adipose tissue in obese male rats. Nutrients. 2020;12(4):925.
  22. Nori P, Haghshenas R, Aftabi Y, Akbari H. Comparison of moderate-intensity continuous training and high-intensity interval training effects on the Ido1-KYN-Ahr axis in the heart tissue of rats with occlusion of the left anterior descending artery. Sci Rep. 2023;13(1):3721.
  23. Cheng Y, Qiu F, Tashiro S, Onodera S, Ikejima T. ERK and JNK mediate TNFalpha-induced p53 activation in apoptotic and autophagic L929 cell death. Biochem Biophys Res Commun. 2008;376(3):483-8.
  24. Hori M, Nishida K. Oxidative stress and left ventricular remodelling after myocardial infarction. Cardiovasc Res. 2009;81(3):457-64.
  25. Sena S, Hu P, Zhang D, Wang X, Wayment B, Olsen C, et al. Impaired insulin signaling accelerates cardiac mitochondrial dysfunction after myocardial infarction. J Mol Cell Cardiol. 2009;46(6):910-8.
  26. Tsutsui H, Kinugawa S, Matsushima S. Mitochondrial oxidative stress and dysfunction in myocardial remodelling. Cardiovasc Res. 2009;81(3):449-56.
  27. Frederico MJ, Justo SL, Da Luz G, Da Silva S, Medeiros C, Barbosa VA, et al. Exercise training provides cardioprotection via a reduction in reactive oxygen species in rats submitted to myocardial infarction induced by isoproterenol. Free Radic Res. 2009;43(10):957-64.
  28. Chen L, Gong Q, Stice JP, Knowlton AA. Mitochondrial OPA1, apoptosis, and heart failure. Cardiovasc Res. 2009;84(1):91-9.
  29. Muthusamy VR, Kannan S, Sadhaasivam K, Gounder SS, Davidson CJ, Boehme C, et al. Acute exercise stress activates Nrf2/ARE signaling and promotes antioxidant mechanisms in the myocardium. Free Radic Biol Med. 2012;52(2):366-76.
  30. Ventura-Clapier R, Garnier A, Veksler V. Transcriptional control of mitochondrial biogenesis: The central role of PGC-1alpha. Cardiovasc Res. 2008;79(2):208-17.
  31. Daussin FN, Zoll J, Dufour SP, Ponsot E, Lonsdorfer-Wolf E, Doutreleau S, et al. Effect of interval versus continuous training on cardiorespiratory and mitochondrial functions: Relationship to aerobic performance improvements in sedentary subjects. Am J Physiol Regul Integr Comp Physiol. 2008;295(1):R264-72.
  32. Haram PM, Kemi OJ, Lee SJ, Bendheim MO, Al-Share QY, Waldum HL, et al. Aerobic interval training vs. continuous moderate exercise in the metabolic syndrome of rats artificially selected for low aerobic capacity. Cardiovasc Res. 2009;81(4):723-32.
  33. Palaniyandi SS, Qi X, Yogalingam G, Ferreira JC, Mochly-Rosen D. Regulation of mitochondrial processes: A target for heart failure. Drug Discov Today Dis Mech. 2010;7(2):e95-102.
  34. Pillai VB, Sundaresan NR, Jeevanandam V, Gupta MP. Mitochondrial SIRT3 and heart disease. Cardiovasc Res. 2010;88(2):250-6.
  35. Guimaraes GV, Ciolac EG, Carvalho VO, D’Avila VM, Bortolotto LA, Bocchi EA. Effects of continuous vs. interval exercise training on blood pressure and arterial stiffness in treated hypertension. Hypertens Res. 2010;33(6):627-32.
مجله دانشکده پزشکی دانشگاه علوم پزشکی مشهد
دوره 68، شماره 5
آذر-دی1404
آذر و دی 1404
صفحه 1421-1434

فایل ها

هم رسانی

ارجاع به این مقاله

آمار