تاثیر تمرین شنا بر فعالیت متالوپروتئنیاز2 و سطوح فاکتور نکروز دهنده تومور آلفا بافت کبد موش های صحرایی دیابتی شده با آلوکسان

نویسندگان

1 گروه تربیت بدنی، دانشگاه آزاد اسلامی واحد قائمشهر، قائم شهر، ایران

2 گروه تربیت بدنی، دانشگاه آزاد اسلامی واحد ساری، ساری، ایران

چکیده

مقدمه و هدف: بیماری کبدی در دیابت نوع 2 رواج دارد و فعالیت ورزشی در پیشگیری و درمان آسیب کبدی ناشی از دیابت مؤثر است. لذا هدف از مطالعه حاضر بررسی تأثیر تمرین شنا بر فعالیت ماتریکس متالوپروتئنیاز 2 (MMP-2) و سطوح فاکتور نکروز دهنده تومور آلفا (TNF-α) در بافت کبد موش‌های صحرایی دیابتی شده با آلوکسان بود.
 
مواد و روش‌ها: در این تحقیق تجربی، 28 سر موش صحرایی نر ویستار به صورت تصادفی به 4 گروه (7 تایی) کنترل، دیابت، تمرین، دیابت+ تمرین تقسیم شدند. دیابت با تزریق درون صفاقی آلوکسان (یک دوز،90 میلی‌گرم/کیلوگرم) القا شد. حیوانات با تمرین شنا به مدت 6 تا 30 دقیقه در روز به مدت 8 هفته ورزش داده شدند و 48 ساعت پس از آخرین مداخله‌ها کشته شدند و فعالیت کبدی MMP-2 و سطوح TNF-α به ترتیب به روش‌های زیموگرافی و الایزا تعیین شد. از آزمون آنالیز واریانس یک طرفه برای تجزیه و تحلیل دادها استفاده شد (05/0>p < /span>).
 
نتایج: یافته‌ها نشان داد متعاقب القای دیابت، فعالیت MMP-2 و سطوح TNF-α کبدی در موش‌های صحرایی افزایش یافت (05/0>p < /span>) درحالی‌که 8 هفته تمرین شنا منجر به کاهش معنی‌دار سطوح TNF-α و فعالیت MMP-2 در بافت کبد موش‌های صحرایی دیابتی شد (05/0>p < /span>).
 
نتیجه‌گیری: به نظر می‌رسد تمرین منظم شنا می‌تواند به واسطه کاستن از فعالیت MMP-2 و سطح بیان TNF-α در موش‌های صحرایی دیابتی تا حدودی از آسیب کبدی ناشی از دیابت جلوگیری کند.
 

کلیدواژه‌ها


عنوان مقاله [English]

The effect of swimming exercise on the Matrix mettaloproteinase 2 activity and tumor necrosis factor-α levels of liver tissue in Alloxan-induced diabetic rats

نویسندگان [English]

  • Masoumeh Habibian 1
  • Aniceh Amanian 2
چکیده [English]

Background and Objective: liver disease is highly prevalent in type 2 diabetes mellitus (T2DM) and exercise training is effective in preventing and treating diabetes-induced hepatic injury. Therefore, the aim of this study was to assess the effect of chronic swimming exercise on the hepatic matrix metalloproteinase 2 (MMP-2) activity and tumor necrosis factor-α (TNF-α) level of liver tissue in alloxan-induced diabetic rats.
 
Materials and Methods: In this study, 28 male Wistar rats were randomly divided into 4 groups (7 rats per group) of control, diabetes, exercise, and diabetes-exercise. Diabetes was induced by alloxan (90 mg/kg, i.p.). The animals exercised by swimming training at 5 min to 30 min per day, five days a week over 8 weeks. The rats were killed 48 h after the last treatments and liver MMP-2 and TNF-α level were evaluated by zymography and  ELISA methods. One-way analysis of variance was used for data analysis.
 
Results: Findings showed that the diabetes significantly increases MMP-2 activity and TNF-α level in animals (p˂0.05). In addition, 8 weeks swimming training were associated with a significant decrease of TNF-α level and MMP-2 activity in the liver tissue of diabetic rats (p˂0.05).
 
Conclusion: It seems that regular swimming training can partially prevent diabetes-induced liver injury via decreasing MMP-2 activity and TNF-α level in diabetic rats.

کلیدواژه‌ها [English]

  • Diabetes mellitus
  • Matrix metalloproteinase 2
  • Exercise
  • Tumor
1. Bhatt HB, Smith RJ. Fatty liver disease in diabetes mellitus. Hepatobiliary Surgery and Nutrition 2015;4(2):101-108. 2. Tolman KG, Fonseca V, Dalpiaz A, Tan MH. Spectrum of liver disease in type 2 diabetes and management of patients with diabetes and liver disease. Diabetes Care 2007;30(3);734-43. 3. Lee BH, Hsu WH, Hsu YW, Pan TM. Suppression of dimerumic acid on hepatic fibrosis caused from carboxymethyl-lysine (CML) by attenuating oxidative stress depends on Nrf2 activation in hepatic stellate cells (HSCs). Food and Chemical Toxicology 2013;62:413-9. 4. Hsu WH, Lee BH, Hsu YW, Pan TM. Peroxisome proliferator-activated receptor-γ activators monascin and rosiglitazone attenuate carboxymethyllysine-induced fibrosis in hepatic stellate cells through regulating the oxidative stress pathway but independent of the receptor for advanced glycation end products signaling. Journal of Agricultural and Food Chemistry 2013;61(28):6873-9. 5. Duarte S, Baber J, Fujii T, Coito AJ. Matrix metalloproteinases in liver injury, repair and fibrosis. Matrix Biology 2015;44-46:147-56. 6. Radbill BD, Gupta R, Ramirez MC, DiFeo A, Martignetti JA, AlvarezCE, et al. Loss of matrixmetalloproteinase-2 amplifies murine toxin-induced liver fibrosis by upregulating collagen I expression. Digestive Diseases and Sciences 2011;56(2):406-16. 7. Iway S, KamiyaY, Tsujiyama K, Murayama M, Tsuchiya H, Tomita Y, et al. Effect of Green Tea on the mRNA Expression of Matrix Metalloproteinases in the Liver and Kidney of Diabetic Rats. The Showa University Journal of Medical Sciences 2008;20(1): 11-20. 8. Salama SM, Abdull MA, AlRashdi AS, Hadi AH. Mechanism of Hepatoprotective Effect of Boesenbergia rotunda in Thioacetamide-Induced Liver Damage in Rats. Evidence-Based Complementary and Alternative Medicine 2013;2013:157456. 9. He Q, Li JK, Li F, Li RG, Zhan GQ, Li G, et al. Mechanism of action of gypenosides on type 2 diabetes and non-alcoholic fatty liver disease in rats. World Journal of Gastroenterology 2015;21(7):2058-66. 10. Kawanishi N, Yano H, Mizokami T, Takahashi M, Oyanagi E, Suzuki K. Exercise training attenuates hepatic inflammation, fibrosis and macrophage infiltration during diet induced-obesity in mice. Brain, Behavior, and Immunity 2012;26(6):931-41. 11. Ayepola OR, Chegou NN, Brooks NL, Oguntibeju OO. Kolaviron, a Garcinia biflavonoid complex ameliorates hyperglycemia-mediated hepatic injury in rats via suppression of inflammatory responses. BMC Complementary and Alternative Medicine 2013(363); 13:1-9. 12. Li L, Li L, Chen L, Lin X, Xu Y, Ren J, et al. Effect of oleoylethanolamide on diet-induced nonalcoholic fatty liver in rats. Journal of Pharmacological Sciences 2015;127(3):244-50. 13. Tai CJ, Choong CY, Shi YC, Lin YC, Wang CW, Lee BH, et al. Solanum nigrum Protects against Hepatic Fibrosis via Suppression of Hyperglycemia in High-Fat/Ethanol Diet-Induced Rats. Molecules 2016;21(3):269. 14. Johnson NA, Keating SE, George J. Exercise and the liver: implications for therapy in fatty liver disorders. Seminars in Liver Disease 2012;32(1):65-79. 15. Schultz A, Mendonca LS, Aguila MB, Mandarim-de-Lacerda CA. Swimming training beneficial effects in a mice model of nonalcoholic fatty liver disease. Experimental and Toxicologic Pathology 2012;64(4):273-8210. 16. Esposito E, Iacono A, Bianco G, Autore G, Cuzzocrea S, Vajro P, et al. Probiotics reduce the inflammatory response induced by a high-fat diet in the liver of young rats. Journal of Nutrition 2009;139(5):905-11. 17. Khosravi M, Habibian M.The effect of 8 weeks regular swimming exercise on the cardiac levels of Matrix mettaloproteinase-2 and transforming growth factor-β1 in diabetic rats. Iranian Journal of Diabetes and Metabolism 2016; 15(2):67-84. (Persian). 18. Peng CC, Chen KC, Hsieh CLan, Peng RY. Swimming Exercise Prevents Fibrogenesis in Chronic Kidney Disease by Inhibiting the Myofibroblast Transdifferentiation. PLoS ONE 2012; 7(6): e37388:1-17. 19. Palladini G, Ferrigno A, Rizzo V, Tarantola E, Bertone V, Freitas I, et al. Lung Matrix Metalloproteinase Activation following Partial Hepatic Ischemia/Reperfusion Injury in Rats. Scientific World Journal 2014;2014:867548. 20. Zhang H, HeY, Chung PK, Tong TK, Fu FH, ChenY, et al. Effects of 12 Weeks of Exercise on Hepatic TNF-α and PPARα in an Animal Model of High-Fat Diet-Induced Nonalcoholic Steatohepatitis. Journal of Exercise Science & Fitness 2009;7(1): 18-23. 21. Knobler H, Schattner A. TNF-α, chronic hepatitis C and diabetes: a novel triad. Quarterly Journal of Medicine 2005;98(1):1-6. 22. Tilg H, Diehl AM. Cytokines in alcoholic and nonalcoholic steatohepatitis. The New England Journal of Medicine 2000; 343(20):1467–1476. 23. Boden G, Song W, Kresge K, Mozzoli M, Cheung P. Effects of hyperinsulinemia on hepatic metalloproteinases and their tissue inhibitors. American Journal of Physiology - Endocrinology and Metabolism 2008; 295(3): E692–E697. 24. Romagnoli M, Gomez-Cabrera MC, Perrelli MG, Biasi F, Pallardó FV, Sastre J, et al. Xanthine oxidase-induced oxidative stress causes activation of NF-kappaB and inflammation in the liver of type I diabetic rats. Free Radical Biology & Medicine 2010;49(2):171-7. 25. Zhang X, Li Z, Liu D, Xu X, Shen W, Mei Z. Effects of probucol on hepatic tumor necrosis factor-alpha, interleukin-6 and adiponectin receptor-2 expression in diabetic rats. Journal of Gastroenterology and Hepatology 2009;24(6):1058-63. 26. Pektaş MB, Sadi G, Koca HB, Yuksel Y, Vurmaz A, Koca T, et al. Resveratrol Ameliorates the Components of Hepatic Inflammation and Apoptosis in a Rat Model of Streptozotocin-Induced Diabetes. Drug Development Research 2016;77(1):12-9. 27. Sodhi K, Puri N, Favero G, Stevens S, Meadows C, Abraham NG, et al. Fructose Mediated Non-Alcoholic Fatty Liver Is Attenuated by HO-1-SIRT1 Module in Murine Hepatocytes and Mice Fed a High Fructose Diet. PLoS One 2015;10(6):e0128648. 28. Habibian M, Saghafi MR, Farzanegi P. The Effect of Regular Swimming Exercise on the Levels of Renal Matrix Mettaloproteinase-2 and Transforming Growth Factor-β1 in Rats with Diabetes. Journal of Kerman University of Medical Sciences 2016; 23(4): 446-456. (Persian). 29. Kwak HB, Kim JH, Joshi K, Yeh A, Martinez DA, Lawler JM. Exercise training reduces fibrosis and matrix metalloproteinase dysregulation in the aging rat heart. Federation of American Societies for Experimental Biology Journal 2011;25(3):1106-17. 30. Iway S, KamiyaY, Tsujiyama K, Murayama M, Tsuchiya H, Tomita Y, et al Effect of Green Tea on the mRNA Expression of Matrix Metalloproteinases in the Liver and Kidney of Diabetic Rats. The Showa University Journal of Medical Sciences 2009;20(1): 11-20. 31. Peng J, Li X, Feng Q, Chen L, Xu L, Hu Y. Anti-fibrotic effect of Cordyceps sinensis polysaccharide: Inhibiting HSC activation, TGF-β1/Smad signalling, MMPs and TIMPs. Experimental Biology and Medicine 2013;238(6):668-77. 32. Palladini G, Ferrigno A, Richelmi P, Perlini S, Vairetti M.Role of matrix metalloproteinases in cholestasis and hepatic ischemia/reperfusion injury: A review. World Journal of Gastroenterology 2015; 21(42): 12114-12124. 33. Guo R, Liong EC, So KF, Fung ML, Tipoe GL. Beneficial mechanisms of aerobic exercise on hepatic lipid metabolism in non-alcoholic fatty liver disease. Hepatobiliary & Pancreatic Diseases International 2015;14(2):139-44.