血流限制抗阻训练通过抑制TGF-β1/Smad3 信号通路减轻2型糖尿病大鼠肾纤维化.

AIM: To investigate the improvement effect of blood flow-limited resistance training on renal fibrosis in type 2 diabetes mellitus (T2DM) rats and its potential mechanism to attenuate renal fibrosis by inhibiting the trans⁃ forming growth factor β1 (TGF-β1)/Smad3 signaling pathway. METHODS: The T2DM model was prepared by combining a high-fat diet and streptozotocin (STZ), and after successful modeling, the rats were randomly divided into a T2DM control group, a low-load resistance training group, a high-load resistance training group, a blood flow restriction group and a blood flow restriction combined with resistance training group for 8 weeks of exercise. The renal index, fasting blood glucose (FBG), serum creatinine (SCr), and blood urea nitrogen (BNU) were recorded in each group. The morphological changes of the kidneys were observed by hematoxylin and eosin (HE) and Masson’s trichrome staining, and the collagen volume fraction was calculated. The mRNA expression levels of renal Klotho, TGF-β1, and α-smooth muscle actin (α -SMA) were detected by RT-qPCR. The protein expression levels of renal Klotho, TGF- β1, Smad3, phosphorylated Smad3 (p-Smad3), α-SMA and connective tissue growth factor (CTGF) were detected using Western blot. RESULTS: Compared with the other groups, FBG, SCr, BNU, and renal collagen volume fraction were significantly decreased in the blood flow restriction combined with resistance training group of rats (P<0. 05), Klotho expression was significantly increased (P<0. 05), and the expression of TGF-β1, p-Smad3, CTGF and α-SMA was significantly decreased (P<0. 05), and there was no significant change in the expression level of Smad3 (P>0. 05). CONCLUSION: Blood flow restriction combined with resistance training attenuates renal fibrosis in T2DM rats, the mechanism of which may be related to the up-regulation of Klotho expression, disruption of the TGF-β1/Smad3 signaling pathway, and inhibition of the deposition of epithelial-mesenchymal transformation. [ABSTRACT FROM AUTHOR]