اثر 8 هفته تمرین تناوبی با شدت بالا بر میزان پروتئین های Wnt و NF-kB بافت قلب موش های صحرایی نر نژاد ویستار مبتلا به دیابت نوع 2

رمی, محمد; عظیم پور, مریم; خرمی پور, کیوان

doi:10.52547/joeppa.15.4.19

اثر 8 هفته تمرین تناوبی با شدت بالا بر میزان پروتئین های Wnt و NF-kB بافت قلب موش های صحرایی نر نژاد ویستار مبتلا به دیابت نوع 2

نوع مقاله : علمی - پژوهشی

نویسندگان

¹ گروه فیزیولوژی ورزشی، دانشکده علوم ورزشی، دانشگاه شهید چمران اهواز، اهواز، ایران

² فیزیولوژی ورزشی، گرایش عصبی عضلانی، فسا، ایران

³ دانشکده پزشکی افضلی پور، مرکز تحقیقات فیزیولوژی و علوم اعصاب، پژوهشکده نوروفارماکولوژی، دانشگاه علوم پزشکی کرمان، کرمان، ایران

10.52547/joeppa.15.4.19

چکیده

زمینه و هدف: کاردیومیوپاتی دیابتی یکی از عوامل خطرزای اصلی برای عوارض قلبی- عروقی دیابت است و از آنجایی که فعالیت بدنی در بیماران دیابتی می‌تواند ساختار و عملکرد میوکارد را تحت تأثیر قرار دهد، لذا هدف از پژوهش حاضر بررسی تأثیر هشت هفته تمرین تناوبی با شدت بالا (HIIT) بر محتوای پروتئین‌های NF-kB و Wnt بافت عضله قلبی موش‌های صحرایی نژاد ویستار مبتلا به دیابت نوع دو است.
مواد و روش‌‌ها: در مطالعه حاضر 20 سر موش صحرایی نر نژاد ویستار با سن 8-6 هفته و میانگین وزن 9/16±3/191 گرم، بهطور تصادفی به چهار گروه (هر گروه شامل 5 موش صحرایی) سالم+کنترل، سالم+تمرین، دیابت+کنترل و دیابت+تمرین تقسیم شدند. پس از یک دوره رژیم غذایی پر چرب و سپس القاء دیابت، حیوانات در گروه‌های سالم+تمرین و دیابت+تمرین قرارداد تمرینی را به مدت ۸ هفته و 5 جلسه در هفته را انجام دادند. ۴۸ ساعت پس از آخرین جلسه تمرینی بافت قلب استخراج شد و بررسی سطوح بیان پروتئین‌های NF-kB و Wnt با استفاده از روش وسترن بلات انجام گرفت. داده‌ها با استفاده از آزمون تحلیل واریانس یک طرفه و آزمون تعقیبی توکی در سطح معناداری کوچکتر از 05/0بررسی شد. همچنین، برای بررسی تغییرات وزن و سطح گلوکز موش‌های صحرایی در مراحل و هفته‌های مختلف تمرینی از آزمون تحلیل واریانس مرکب استفاده گردید.
نتایج: نتایج نشان داد مقادیر نسبی پروتئین های NF-kB و Wnt در گروه‌های دیابت+کنترل و دیابت+تمرین به صورت معنا‌داری نسبت به گروه‌های سالم بیشتر بود (001/0P=). همچنین، میزان پروتئین Wnt در گروه دیابت+تمرین نسبت به گروه‌ دیابت+کنترل به صورت معناداری کمتر بود (001/0P=)، در حالی که میزان پروتئین NF-kB در گروه دیابت+تمرین نسبت به گروه دیابت+کنترل تفاوت معنا‌داری را نشان نداد. نتایج آزمون تحلیل واریانس مرکب در خصوص تغییرات میانگین وزن نشان می‌دهد وزن موش‌های صحرایی در گروه‌های دیابت+کنترل و دیابت+تمرین از زمان آغاز تمرین و استفاده از رژیم غذایی پرچرب تا مرحله قبل از تزریق STZ به صورت معنا‌داری بیشتر (001/0P=) و در هفته پایانی و انتهای قرارداد تمرینی به صورت معنا‌داری کمتر بود (001/0P=). همچنین، سطح قند خون گروه‌های دیابت+کنترل و دیابت+تمرین یک هفته پس از تزریق STZ به صورت معنا‌داری بیشتر (به ترتیب 001/0P= و 003/0P=)، و در پایان قرارداد تمرینی در گروه دیابت+تمرین به صورت معنا‌داری کمتر بود (001/0P=).
نتیجه‌گیری: در نهایت باید اظهار داشت که تمرینات HIIT احتمالا می‌تواند ساختار و عملکرد میوکارد را تحت تأثیر قرار داده و به عنوان راهکاری غیر دارویی امیدوارکننده باشد.

کلیدواژه‌ها

عنوان مقاله [English]

The effect of 8 weeks of High Intensity Interval Training on the Levels of Wnt and NF-κB proteins in the heart tissue of male Wistar rats with type 2 diabetes

نویسندگان [English]

Mohammad Rami ¹
Maryam Azimpour ²
Kayvan Khoramipour ³

¹ Department of Sport Physiology, Faculty of Sport Sciences, Shahid Chamran University of Ahvaz, Ahvaz, Iran

² Sport Physiology, Neuromuscular Orientation, Fasa, Iran

³ Department of Physiology and Pharmacology, Afzalipour Medical Faculty, Physiology Research Center and Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

چکیده [English]

Background and Purpose: Diabetic cardiomyopathy is one of the main risk factors for cardiovascular complications of diabetes and since physical activity in diabetic patients can affect the structure and function of the myocardium, the aim of the present study was to investigate the effect of eight weeks of HIIT training on the content of NF-kB and Wnt proteins in the heart muscle tissue of Wistar rats with type 2 diabetes.
Materials and Methods: In the present study, 20 male Wistar rats were randomly divided into four groups (each group including five rats) Control+Healthy, Exercise+Healthy, Control+Diabetes, and Exercise+Diabetes. After a period of high-fat diet and then after induction of diabetes, animals in Exercise+Diabetes and Exercise+Healthy groups performed the training protocol for eight weeks and five sessions per week. 48 hours after the last training session, cardiac tissue was extracted and the expression levels of NF-kB and Wnt proteins were assessed using Western blotting. Data were analyzed using one-way ANOVA and Tukey post hoc test at a significance level of less than 0.05. Also, mixed ANOVA test was used to evaluate changes in weight and glucose levels of rats in different stages and weeks of training.
Results: The results showed that the relative Levels of NF-kB and Wnt proteins in Control+Diabetes and Exercise+Eiabetes groups is significantly more than healthy groups (P = 0.001). Also, the Levels of Wnt protein in the Exercise+Diabetes group was significantly less than the Control+Diabetes group (P = 0.001), While the Levels of NF-κB protein in the Exercise+Diabetes group did not show a significant difference compared to the Control+Diabetes group. The results of mixed ANOVA test on mean weight changes show that the weight of rats in Control+Diabetes and Exercise+Diabetes groups was significantly higher (P = 0.001) than the beginning of training and use of high-fat diet to the stage before STZ injection and in the last week. In addition, at the end of the training protocol was significantly became less (P = 0.001). Also, blood glucose levels of Control+Diabetes and Exercise+Diabetes groups was significantly higher (P = 0.001 and 0.003, respectively) at one week after STZ injection and was significantly lower in the Exercise+Diabetes group at the end of the training protocol (P=0.001).
Conclusion: Finally, it should be noted that high-intensity intermittent exercise could potentially affect myocardial structure and function and be promising as a non-pharmacological solution.

کلیدواژه‌ها [English]

HIIT Exercise
Diabetes
Cardiomyopathy
Diet

مراجع

Yang Q, Wang W-w, Ma P, Ma Z-x, Hao M, Adelusi TI. Swimming training alleviated insulin resistance through Wnt3a/β-catenin signaling in type 2 diabetic rats. Iranian journal of basic medical sciences. 2017;20(11):1220.
1. Amrolahi Z, Avandi SM, Khaledi N. The effect of six weeks’ progressive resistance training on hippocampus BDNF gene expression and serum changes of TNF-α in diabetic wistar rats. Journal of Sport and Exercise Physiology. 2022:1-10.
2. Zhang Z, Zhang D, Dou M, Li Z, Zhang J, Zhao X. Dendrobium officinale Kimura et Migo attenuates diabetic cardiomyopathy through inhibiting oxidative stress, inflammation and fibrosis in streptozotocin-induced mice. Biomedicine & Pharmacotherapy. 2016;84:1350-8.
3. Shadmehri S, Sharafati Moghadam M. The effect of four weeks high-intensity interval training (HIIT) on the content of AKT1, mTOR, P70S6K1, 4EBP1 proteins in the Left ventricular muscle tissue of the heart obese rats with type 2 diabetic. Journal of Sport and Exercise Physiology. 2021;14(1):85-94.
4. Liu Q, Wang S, Cai L. Diabetic cardiomyopathy and its mechanisms: role of oxidative stress and damage. Journal of diabetes investigation. 2014;5(6):623-34.
5. Wan A, Rodrigues B. Endothelial cell–cardiomyocyte crosstalk in diabetic cardiomyopathy. Cardiovascular research. 2016;111(3):172-83.
6. Rajesh M, Mukhopadhyay P, Bátkai S, Patel V, Saito K, Matsumoto S, et al. Cannabidiol attenuates cardiac dysfunction, oxidative stress, fibrosis, and inflammatory and cell death signaling pathways in diabetic cardiomyopathy. Journal of the American College of Cardiology. 2010;56(25):2115-25.
7. Liu J-j, Shentu L-m, Ma N, Wang L-y, Zhang G-m, Sun Y, et al. Inhibition of NF-κB and Wnt/β-catenin/GSK3β signaling pathways ameliorates cardiomyocyte hypertrophy and fibrosis in streptozotocin (STZ)-induced type 1 diabetic rats. Current Medical Science. 2020;40(1):35-47.
8. Zheng X, Zhu S, Chang S, Cao Y, Dong J, Li J, et al. Protective effects of chronic resveratrol treatment on vascular inflammatory injury in streptozotocin-induced type 2 diabetic rats: Role of NF-kappa B signaling. European Journal of Pharmacology. 2013;720(1-3):147-57.
9. Mong M-c, Yin M-c. Nuclear factor κB-dependent anti-inflammatory effects of s-allyl cysteine and s-propyl cysteine in kidney of diabetic mice. Journal of agricultural and food chemistry. 2012;60(12):3158-65.
10. Halder SK, Sharan C, Al-Hendy A. 1, 25-dihydroxyvitamin D3 treatment shrinks uterine leiomyoma tumors in the Eker rat model. Biology of reproduction. 2012;86(4):116, 1-10.
11. Bagul PK, Deepthi N, Sultana R, Banerjee SK. Resveratrol ameliorates cardiac oxidative stress in diabetes through deacetylation of NFkB-p65 and histone 3. The Journal of nutritional biochemistry. 2015;26(11):1298-307.
12. Yang Y, Lv J, Jiang S, Ma Z, Wang D, Hu W, et al. The emerging role of Toll-like receptor 4 in myocardial inflammation. Cell death & disease. 2016;7(5):e2234-e.
13. Elçioğlu HK, Kabasakal L, Özkan N, Çelikel Ç, Ayanoğlu-Dülger G. A study comparing the effects of rosiglitazone and/or insulin treatments on streptozotocin induced diabetic (type I diabetes) rat aorta and cavernous tissues. European journal of pharmacology. 2011;660(2-3):476-84.
14. Dawson K, Aflaki M, Nattel S. Role of the Wnt‐Frizzled system in cardiac pathophysiology: a rapidly developing, poorly understood area with enormous potential. The Journal of physiology. 2013;591(6):1409-32.
15. Liu X, Chen D, Wu Z, Li J, Li J, Zhao H, et al. Ghrelin inhibits high glucose-induced 16HBE cells apoptosis by regulating Wnt/β-catenin pathway. Biochemical and biophysical research communications. 2016;477(4):902-7.
16. Zhang M, Ye M. Hydrogen sulfide attenuates high glucose-induced myocardial injury in rat cardiomyocytes by suppressing wnt/beta-catenin pathway. Current Medical Science. 2019;39(6):938-46.
17. Chong Z, Maiese K. Targeting WNT, protein kinase B, and mitochondrial membrane integrity to foster cellular survival in the nervous system. Histology and histopathology. 2004;19(2):495.
18. Schmederer Z, Rolim N, Bowen TS, Linke A, Wisloff U, Adams V, et al. Endothelial function is disturbed in a hypertensive diabetic animal model of HFpEF: moderate continuous vs. high intensity interval training. International journal of cardiology. 2018;273:147-54.
19. 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. Archives of physiology and biochemistry. 2020;126(3):250-7.
20. Beavers KM, Brinkley TE, Nicklas BJ. Effect of exercise training on chronic inflammation. Clinica chimica acta. 2010;411(11-12):785-93.
21. Khademi Y, Azarbayjani M, Hosseini H. Simultaneous effect of high-intensity interval training (HIIT) and consumption of flaxseed on serum levels of TNF-α and IL1β in rats. The Horizon of Medical Sciences. 2017;23(4):257-63.
22. Alvarez C, Ramirez-Campillo R, Martinez-Salazar C, Mancilla R, Flores-Opazo M, Cano-Montoya J, et al. Low-volume high-intensity interval training as a therapy for type 2 diabetes. International journal of sports medicine. 2016;37(09):723-9.
23. Little JP, Gillen JB, Percival ME, Safdar A, Tarnopolsky MA, Punthakee Z, et al. Low-volume high-intensity interval training reduces hyperglycemia and increases muscle mitochondrial capacity in patients with type 2 diabetes. Journal of applied physiology. 2011;111(6):1554-60.
24. Hansen D, Dendale P, Jonkers R, Beelen M, Manders R, Corluy L, et al. Continuous low-to moderate-intensity exercise training is as effective as moderate-to high-intensity exercise training at lowering blood HbA1c in obese type 2 diabetes patients. Diabetologia. 2009;52(9):1789-97.
25. Kukulski F, Lévesque SA, Sévigny J. Impact of ectoenzymes on p2 and p1 receptor signaling. Advances in pharmacology. 2011;61:263-99.
26. Calegari L, Nunes RB, Mozzaquattro BB, Rossato DD, Dal Lago P. Exercise training improves the IL-10/TNF-α cytokine balance in the gastrocnemius of rats with heart failure. Brazilian journal of physical therapy. 2018;22(2):154-60.
27. Sugimoto K, Rashid IB, Shoji M, Suda T, Yasujima M. Early changes in insulin receptor signaling and pain sensation in streptozotocin-induced diabetic neuropathy in rats. The Journal of pain. 2008;9(3):237-45.
28. Ramezani N, Vanaky B, Shakeri N, Soltanian Z, Fakhari Rad F, Shams Z. Evaluation of Bcl-2 and Bax Expression in the Heart of Diabetic Rats after Four Weeks of High Intensity Interval Training. Medical Laboratory Journal. 2019;13(1):15-20.
29. Tsai S-J, Huang C-S, Mong M-C, Kam W-Y, Huang H-Y, Yin M-C. Anti-inflammatory and antifibrotic effects of naringenin in diabetic mice. Journal of agricultural and food chemistry. 2012;60(1):514-21.
30. Martinez A, Castro A, Dorronsoro I, Alonso M. Glycogen synthase kinase 3 (GSK‐3) inhibitors as new promising drugs for diabetes, neurodegeneration, cancer, and inflammation. Medicinal research reviews. 2002;22(4):373-84.
31. Hie M, Iitsuka N, Otsuka T, Tsukamoto I. Insulin-dependent diabetes mellitus decreases osteoblastogenesis associated with the inhibition of Wnt signaling through increased expression of Sost and Dkk1 and inhibition of Akt activation. International journal of molecular medicine. 2011;28(3):455-62.
32. Saraswati S, Alfaro MP, Thorne CA, Atkinson J, Lee E, Young PP. Pyrvinium, a potent small molecule Wnt inhibitor, promotes wound repair and post-MI cardiac remodeling. PloS one. 2010;5(11):e15521.
33. Xi X-H, Wang Y, Li J, Wang F-W, Tian G-H, Yin M-S, et al. Activation of Wnt/β-catenin/GSK3β signaling during the development of diabetic cardiomyopathy. Cardiovascular Pathology. 2015;24(3):179-86.
34. Hu Y, Gu X, Li R, Luo Q, Xu Y. Glycogen synthase kinase-3β inhibition induces nuclear factor-κB-mediated apoptosis in pediatric acute lymphocyte leukemia cells. Journal of Experimental & Clinical Cancer Research. 2010;29(1):1-8.
35. Fayaz E, Damirchi A, Zebardast N, Babaei P. Cinnamon extract combined with high-intensity endurance training alleviates metabolic syndrome via non-canonical WNT signaling. Nutrition. 2019;65:173-8.
36. Wang L, Lavier J, Hua W, Wang Y, Gong L, Wei H, et al. High-intensity interval training and moderate-intensity continuous training attenuate oxidative damage and promote myokine response in the skeletal muscle of ApoE KO mice on high-fat diet. Antioxidants. 2021;10(7):992.
37. Liu H-W, Chang S-J. Moderate exercise suppresses NF-κB signaling and activates the SIRT1-AMPK-PGC1α axis to attenuate muscle loss in diabetic db/db mice. Frontiers in physiology. 2018;9:636.
38. Holloway TM, Bloemberg D, da Silva ML, Simpson JA, Quadrilatero J, Spriet LL. High intensity interval and endurance training have opposing effects on markers of heart failure and cardiac remodeling in hypertensive rats. PloS one. 2015;10(3):e0121138.
39. Ma JK, Scribbans TD, Edgett BA, Boyd JC, Simpson CA, Little JP, et al. Extremely low-volume, high-intensity interval training improves exercise capacity and increases mitochondrial protein content in human skeletal muscle. Open Journal of Molecular and Integrative Physiology. 2013;2013.