تاثیر تمرینات تناوبی شدید به همراه تزریق ویتامین دی3 بر التهاب ناشی از اتوفاژی بیش از حد در بافت قلب موش های دیابتی نوع 2

مقالات آماده انتشار

نوع مقاله : مقاله پژوهشی Released under (CC BY-NC 4.0) license I Open Access I

نویسندگان

1 گروه فیزیولوژی ورزشی، دانشکده علوم انسانی و اجتماعی، دانشگاه کردستان، سنندج، ایران.

2 گروه فیزیولوژی ورزشی، دانشکده علوم انسانی و اجتماعی، دانشگاه کردستان، کردستان، ایران

چکیده

زمینه و هدف: اتوفاژی بیش از حد، همراه با التهاب، یک ویژگی پاتولوژیک کلیدی است که در اختلال عملکرد قلبی در دیابت نوع 2 (T2D) دخیل است. این مطالعه با هدف بررسی اثرات تمرین تناوبی با شدت بالا (HIIT) همراه با مکمل ویتامین د3 بر التهاب و اتوفاژی در بافت قلب رت‌های صحرایی القا شده با T2D انجام شد. روش پژوهش: چهل سر رت نر نژاد ویستار از طریق ترکیبی از رژیم غذایی پرچرب و تزریق استرپتوزوتوسین (STZ) با دوز پایین به T2D القا شدند سپس حیوانات به چهار گروه (8 سر) کنترل سالم، کنترل دیابت، دیابت+ HIIT، دیابت+ ویتامین د3 و دیابت+ HIIT و ویتامین د3 تقسیم شدند. پروتکل HIIT برای هشت هفته، 3 جلسه در هفته، با شدت90-85% حداکثر سرعت دویدن از طریق دویدن روی تردمیل اجرا شد. ویتامین د3 (25/0 میلی گرم/کیلوگرم) به صورت هفتگی تزریق شد. در پایان دوره مداخلات، بافت قلب از نظر محتوای نشانگر اتوفاژی ULK-1، نشانگرهای التهابی NF-kB و اینترلوکین-6 (IL-6)، و سطوح سرمی گلوکز و شاخص مقاومت به انسولین مورد بررسی قرار گرفت. یافته‌ها: نتایج نشان داد که T2D به طور قابل توجهی سطوح ULK-1، NF-kB و IL-6 را در بافت قلب افزایش می‌دهد، که نشان‌دهنده اتوفاژی بیش از حد است (001/0=P). با این حال، هشت هفته HIIT، چه با مکمل و چه بدون مکمل ویتامین د3، به طور قابل توجهی این نشانگرها را کاهش داد (001/0=P). قابل ذکر است، ترکیب HIIT و تزریق ویتامین د3 بیشترین کاهش را در نشانگرهای اتوفاژی و التهاب نشان داد. همچنین، این مداخلات سطح سرمی گلوکز و مقاومت به انسولین را بهبود بخشید (001/0=P). نتیجه‌گیری: ترکیبی از HIIT و تزریق ویتامین د3 به طور موثر التهاب و اتوفاژی بیش از حد در بافت قلبی رت‌های T2D را کاهش می‌دهد و یک استراتژی درمانی بالقوه برای جلوگیری از عوارض قلبی عروقی در بیماران T2D را پیشنهاد می‌کند.

کلیدواژه‌ها

موضوعات

عنوان مقاله [English]

The Effect of High Intensity Interval Training along with Vitamin D3 Injection on Inflammation Caused by Excessive Autophagy in Heart Tissue of Type 2 Diabetic Rats

نویسندگان [English]

  • Hadi Golpasandi 1
  • Mohammad Rahman Rahimi 2
1 Department of Exercise Physiology, Faculty of Humanities and Social Sciences, University of Kurdistan, Sanandaj, Iran
2 Department of Exercise Physiology, Faculty of Humanities and Social Sciences, University of Kurdistan, Sanandaj, Iran
چکیده [English]

Background& purpose: Excessive autophagy, together with inflammation, is a key pathological feature contributing to cardiac dysfunction in type 2 diabetes (T2D). This study aimed to investigate the effects of high-intensity interval training (HIIT) with vitamin D3 supplementation on inflammation and autophagy in heart tissue of T2D-induced rats. Methods: Forty male Wistar rats were induced to T2D through a combination of high-fat diet and low-dose streptozotocin (STZ) injection. After the induction of T2D, the animals were divided into four groups (N=8): Normal control, diabetes control, diabetes + HIIT, diabetes + vitamin D3 and diabetes + HIIT and vitamin D3. The HIIT protocol was performed for eight weeks, 3 sessions per week, with an intensity of 90-85% of maximum running speed through treadmill running. Vitamin D3 (0.25 mg.kg-1) was injected weekly. At the end of the intervention period, heart tissue was evaluated for the content of autophagy marker ULK-1, inflammatory markers NF-kB and interleukin-6 (IL-6), and serum glucose levels and insulin resistance index. Results: The results showed that T2D significantly increases the levels of ULK-1, NF-κB and IL-6 in heart tissue, which indicates excessive autophagy and inflammation (P=0.001). However, eight weeks of HIIT, with or without vitamin D3 supplementation, significantly reduced these markers (P=0.001). Notably, the combination of HIIT and vitamin D3 injection showed the greatest reduction in autophagy and inflammation markers. Also, these interventions improved serum glucose levels and insulin resistance (P=0.001). Conclusions: A combination of HIIT and vitamin D3 injection effectively reduces inflammation and excessive autophagy in cardiac tissue of T2D rats and suggests a potential therapeutic strategy to prevent cardiovascular complications in T2D patients.

کلیدواژه‌ها [English]

  • Ulk1 protein
  • NF-kappa B
  • Autophagy
  • HIIT
  • type 2 diabetes

مراجع

  1. Heather LC, Gopal K, Srnic N, Ussher JR. Redefining Diabetic Cardiomyopathy: Perturbations in Substrate Metabolism at the Heart of Its Pathology. Diabetes. 2024 May 1;73(5):659-70.
  2. Zhang L, Hu C, Jin B, Bai B, Liao J, Jin L, Wang M, Zhu W, Wu X, Zheng L, Xu X. Bicyclol alleviates streptozotocin-induced diabetic cardiomyopathy by inhibiting chronic inflammation and oxidative stress. Cardiovascular Drugs and Therapy. 2024 Jun;38(3):555-68.
  3. Li Q, Peng G, Liu H, Wang L, Lu R, Li L. Molecular mechanisms of secretory autophagy and its potential role in diseases. Life Sciences. 2024 Apr 23:122653.
  4. Jones SA, Mills KH, Harris J. Autophagy and inflammatory diseases. Immunology and cell biology. 2013 Mar;91(3):250-8.
  5. Davari M, Hashemi R, Mirmiran P, Hedayati M, Sahranavard S, Bahreini S, Tavakoly R, Talaei B. Effects of cinnamon supplementation on expression of systemic inflammation factors, NF-kB and Sirtuin-1 (SIRT1) in type 2 diabetes: a randomized, double blind, and controlled clinical trial. Nutrition journal. 2020 Dec;19:1-8.
  6. Noori Mofrad SR, Golpasandi H, Sakhaei MH, Khalafi M. The effect of high intensity interval training on inflammatory markers in patient with type 2 diabetes: a systematic review and meta-analysis. Journal of Applied Health Studies in Sport Physiology. 2022 Sep 23;9(2):123-37, (In Persian).
  7. Gibala MJ, Little JP, MacDonald MJ, Hawley JA. Physiological adaptations to low‐volume, high‐intensity interval training in health and disease. The Journal of physiology. 2012 Mar 1;590(5):1077-84.
  8. Edwards JJ, Griffiths M, Deenmamode AH, O’Driscoll JM. High-intensity interval training and cardiometabolic health in the general population: a systematic review and meta-analysis of randomised controlled trials. Sports Medicine. 2023 Sep;53(9):1753-63.
  9. Sabouri M, Hatami E, Pournemati P, Shabkhiz F. Inflammatory, antioxidant and glycemic status to different mode of high-intensity training in type 2 diabetes mellitus. Molecular Biology Reports. 2021 Jun;48:5291-304.
  10. Golpasandi H, Rahimi MR, Ahmadi S. The Interactive Effect of Eight Weeks of Aerobic Training and Vitamin D3 Supplementation on Cardiac Irisin Protein Levels, Insulin Resistance and Lipid Profile in Rats Induced with Type 2 Diabetes. Iranian Journal of Diabetes and Metabolism. 2023 Dec 10;23(5):327-37, (In Persian).
  11. Bhutia SK. Vitamin D in autophagy signaling for health and diseases: Insights on potential mechanisms and future perspectives. The Journal of Nutritional Biochemistry. 2022 Jan 1;99:108841.
  12. Golpasandi H, Rahimi MR, Ahmadi S, Łubkowska B, Cięszczyk P. Effects of Vitamin D3 Supplementation and Aerobic Training on Autophagy Signaling Proteins in a Rat Model Type 2 Diabetes Induced by High-Fat Diet and Streptozotocin. Nutrients. 2023 Sep 17;15(18):4024.
  13. Golpasandi H, Rahimi MR, Ahmadi S. Investigating the mutual effects of autophagy and apoptosis in heart tissue of type 2 diabetic rats in interaction with aerobic exercise training and vitamin D3 injection. Journal of Sport and Exercise Physiology. 2024;17(2):34-4(In Persian).
  14. Keshvari R, HABIBIAN M, ASKARI B. The Effect of High-Intensity Interval Training with Vitamin D Intake on Interleukin-10 and Lipid Peroxidation Levels in Overweight Women with Low Vitamin D Status: A Randomized Clinical Trial.
  15. Percie du Sert N, Hurst V, Ahluwalia A, Alam S, Avey MT, Baker M, Browne WJ, Clark A, Cuthill IC, Dirnagl U, Emerson M. The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. Journal of Cerebral Blood Flow & Metabolism. 2020 Sep;40(9):1769-77.
  16. Ali TM, Abo-Salem OM, El Esawy BH, El Askary A. The potential protective effects of diosmin on streptozotocin-induced diabetic cardiomyopathy in rats. The American Journal of the Medical Sciences. 2020 Jan 1;359(1):32-41.
  17. Bedford TG, Tipton CM, Wilson NC, Oppliger RA, Gisolfi CV. Maximum oxygen consumption of rats and its changes with various experimental procedures. Journal of Applied Physiology. 1979 Dec 1;47(6):1278-83.
  18. 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. Molecular medicine reports. 2015 Aug 1;12(2):2374-82.
  19. Mehdipoor M, Damirchi A, Razavi Tousi SM, Babaei P. Concurrent vitamin D supplementation and exercise training improve cardiac fibrosis via TGF-β/Smad signaling in myocardial infarction model of rats. Journal of physiology and biochemistry. 2021 Feb;77:75-84.
  20. Antunes LC, Elkfury JL, Jornada MN, Foletto KC, Bertoluci MC. Validation of HOMA-IR in a model of insulin-resistance induced by a high-fat diet in Wistar rats. Archives of endocrinology and metabolism. 2016;60:138-42.
  21. Kosacka J, Kern M, Klöting N, Paeschke S, Rudich A, Haim Y, Gericke M, Serke H, Stumvoll M, Bechmann I, Nowicki M. Autophagy in adipose tissue of patients with obesity and type 2 diabetes. Molecular and cellular endocrinology. 2015 Jul 5;409:21-32.
  22. Sehrawat A, Mishra J, Mastana SS, Navik U, Bhatti GK, Reddy PH, Bhatti JS. Dysregulated autophagy: a key player in the pathophysiology of type 2 diabetes and its complications. Biochimica et Biophysica Acta (BBA)-molecular basis of Disease. 2023 Apr 1;1869(4):166666.
  23. Öst A, Svensson K, Ruishalme I, Brännmark C, Franck N, Krook H, Sandström P, Kjolhede P, Strålfors P. Attenuated mTOR signaling and enhanced autophagy in adipocytes from obese patients with type 2 diabetes. Molecular medicine. 2010 Jul;16:235-46.
  24. Zhang L, Zhang H, Xie X, Tie R, Shang X, Zhao Q, Xu J, Jin L, Zhang J, Ye P. Empagliflozin ameliorates diabetic cardiomyopathy via regulated branched-chain amino acid metabolism and mTOR/p-ULK1 signaling pathway-mediated autophagy. Diabetology & Metabolic Syndrome. 2023 May 6;15(1):93.
  25. Liu M, Lu S, He W, Zhang L, Ma Y, Lv P, Ma M, Yu W, Wang J, Zhang M, Zhang Y. ULK1-regulated autophagy: A mechanism in cellular protection for ALDH2 against hyperglycemia. Toxicology letters. 2018 Feb 1;283:106-15.
  26. Murase H, Kuno A, Miki T, Tanno M, Yano T, Kouzu H, Ishikawa S, Tobisawa T, Ogasawara M, Nishizawa K, Miura T. Inhibition of DPP-4 reduces acute mortality after myocardial infarction with restoration of autophagic response in type 2 diabetic rats. Cardiovascular Diabetology. 2015 Dec;14:1-6.
  27. Scervino MV, Fortes MA, Vitzel KF, de Souza DR, Murata GM, Santana GO, da Silva EB, Levada‐Pires AC, Kuwabara WM, Loureiro TC, Curi R. Autophagy signaling in hypertrophied muscles of diabetic and control rats. FEBS Open Bio. 2023 Sep;13(9):1709-22.
  28. Tan Y, Zhang Z, Zheng C, Wintergerst KA, Keller BB, Cai L. Mechanisms of diabetic cardiomyopathy and potential therapeutic strategies: preclinical and clinical evidence. Nature Reviews Cardiology. 2020 Sep;17(9):585-607.
  29. Dewanjee S, Vallamkondu J, Kalra RS, John A, Reddy PH, Kandimalla R. Autophagy in the diabetic heart: a potential pharmacotherapeutic target in diabetic cardiomyopathy. Ageing research reviews. 2021 Jul 1;68:101338.
  30. Rajak S, Raza S, Sinha RA. ULK1 signaling in the liver: autophagy dependent and independent actions. Frontiers in cell and developmental biology. 2022 Feb 18;10:836021.
  31. Golpasasndi S, Abdollahpour S, Golpasandi H. High-intensity interval training combined with saffron supplementation modulates stress-inflammatory markers in obese women with type 2 diabetes. Research in Exercise Nutrition. 2022;1(1):55-61.
  32. Salehpoor Z, Jahromi BN, Tanideh N, Nemati J, Akbarzade-Jahromi M, Jahromi MK. High intensity interval training is superior to moderate intensity continuous training in enhancing the anti-inflammatory and apoptotic effect of pentoxifylline in the rat model of endometriosis. Journal of Reproductive Immunology. 2023 Mar 1;156:103832.
  33. Zhang WY, Guo YJ, Wang KY, Chen LM, Jiang P. Neuroprotective effects of vitamin D and 17ß-estradiol against ovariectomy-induced neuroinflammation and depressive-like state: Role of the AMPK/NF-κB pathway. International Immunopharmacology. 2020 Sep 1;86:106734.
  34. Golpasandi H, Rahimi MR, Ahmadi S. The Interactive Effect of Eight Weeks of Aerobic Training and Vitamin D3 Supplementation on Cardiac Irisin Protein Levels, Insulin Resistance and Lipid Profile in Rats Induced with Type 2 Diabetes. Iranian Journal of Diabetes and Lipid Disorders. 2023;23(5):327-37, (In Persian).
  35. Longo M, Scappaticcio L, Cirillo P, Maio A, Carotenuto R, Maiorino MI, Bellastella G, Esposito K. Glycemic control and the heart: the tale of diabetic cardiomyopathy continues. Biomolecules. 2022 Feb 8;12(2):272.
مطالعات کاربردی تندرستی در فیزیولوژی ورزش

مقالات آماده انتشار، پذیرفته شده
انتشار آنلاین از تاریخ 16 آبان 1403

فایل ها

سابقه مقاله

  • تاریخ دریافت: 25 مرداد 1403
  • تاریخ بازنگری: 15 آبان 1403
  • تاریخ پذیرش: 16 آبان 1403

هم رسانی

ارجاع به این مقاله

آمار