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2022, Vol. 26 ›› Issue (8): 1210-1215Treadmill exercise improves the myocardial fibrosis of spontaneous type 2 diabetic mice: an exploration on the functional pathwayChen Xianghe1, Liu Bo1, Yang Kang2, Lu Pengcheng1, Yu Huilin1
Abstract: BACKGROUND: For type 2 diabetes mellitus accompanied by myocardial interstitial fibrosis, although miR-29a closely regulates the transforming growth factor (TGF)-β1/Smads pathway, little is reported about this signaling pathway regulating myocardial interstitial fibrosis in type 2 diabetes. Existing studies have shown that exercise can improve myocardial fibrosis in type 2 diabetes. OBJECTIVE: To investigate the effect of different kinds of exercises on myocardial fibrosis in spontaneous type 2 diabetic mice (KK-Ay mice) and the molecular regulation of miR-29a/TGF-β1 pathway in this process. METHODS: Twenty-four KK-Ay mice, 10 weeks of age, were adaptively fed for 1 week, and randomly divided into KK-Ay control group (KC; 8 mice), KK-Ay swimming group (KY; 8 mice) and KK-Ay treadmill group (KP; 8 mice). Another eight C57BL/6J mice, 10 weeks of age, were selected as normal control group (ZC). KK-Ay mice were given a high-fat diet, and C57BL/6J mice were fed with common feed. The mice in the KY and KP groups were trained for 8 weeks by swimming and running exercise, respectively. Afterwards, the wall of the left ventricle of the mouse was taken, and the change of myocardial fibrosis was detected by Masson staining. The mRNA expression of relevant factors in the myocardium was detected by RT-PCR; the protein level and expression of the relevant factors in the myocardium were detected by ELISA and western blot, respectively. The study protocol was approved by the Animal Ethics Committee of Physical Education School of Yangzhou University with an approval No. YZU-TYXY-31. RESULTS AND CONCLUSION: Compared with the ZC group, the KC group had a significant degree of myocardial interstitial fibrosis; miR-29a mRNA expression and protein level in the myocardium were significantly reduced and TGF-β1, Smad3, Smad4, type I collagen mRNA expression and p-Smad2, p-Smad3, p-Smad4 protein expression were significantly up-regulated (P < 0.05 or P < 0.01), and TGF-β1 and type I collagen protein levels were significantly increased (P < 0.05 or P < 0.01). Compared with the KC group, no significant change in myocardial fibrosis was observed in the KY group; the expression of TGF-β1 and Smad4 mRNAs in the myocardium was significantly down-regulated and the TGF-β1 protein level was significantly reduced (P < 0.05), and other related indicators were not significantly changed. The degree of myocardial fibrosis in the KP group was significantly improved; miR-29a mRNA expression and protein level in the myocardium increased (P < 0.05), TGF-β1, Smad2, Smad3 and COL1 mRNA expression and TGF-β1, COL1 protein levels decreased significantly (P < 0.05 or P < 0.01), and p-Smad2, p-Smad3 and p-Smad4 protein expression was significantly down-regulated (P < 0.05). Compared with the KY group, the myocardial fibrosis of the KP group was significantly improved; miR-29a mRNA expression and protein level in the myocardium were significantly increased (P < 0.05), TGF-β1, COL1 mRNA expression and protein level were significantly reduced (P < 0.05), and p-Smad2, p-Smad3 and p-Smad4 protein expression was significantly down-regulated (P < 0.05 or P < 0.01). To conclude, type 2 diabetic mice have severe myocardial fibrosis. Treadmill exercise inhibits the TGF-β1/Smads pathway by up-regulating miR-29a in the myocardium of T2DM mice to improve myocardial fibrosis, but swimming exercise has no significant effect. Key words:treadmill, swimming, type 2 diabetes mellitus, myocardial fibrosis, miR-29a |