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  

Blood flow restriction combined with resistance training attenuates renal fibrosis in type 2 diabetic rats by inhibiting TGF-β1/Smad3 pathway

作　　者：林秋苹 查宇喆 刘怡然 喻乾 谭朝文 赵彦[1] LIN Qiuping;ZHA Yuzhe;LIU Yiran;YU Qian;TAN Zhaowen;ZHAO Yan(Nanjing Sport Institute,Nanjing 210014,China)

机构地区：[1]南京体育学院,江苏南京210014

出　　处：《中国病理生理杂志》2024年第8期1470-1478,共9页Chinese Journal of Pathophysiology

基　　金：江苏省重点研发计划(No.BE2022828);江苏省运动与健康工程协同创新中心(No.JSCIC-GP21007);2023年江苏省研究生科研与实践创新计划(No.KYCX23_2369)。

摘　　要：目的:探究血流限制抗阻训练对2型糖尿病(T2DM)大鼠肾纤维化的影响及其通过抑制转化生长因子-β1(TGF-β1)/Smad家族成员3(Smad3)信号通路减轻肾纤维化的潜在机制。方法:采用高脂饲料和链脲佐菌素(STZ)联合制备大鼠T2DM模型,造模成功后随机分为T2DM对照(CON,n=5)组、低负荷抗阻训练(LRT,n=5)组、高负荷抗阻训练(HRT,n=5)组、血流限制(BFR,n=5)组和血流限制抗阻训练(BFRT,n=5)组,进行为期8周的运动训练。记录各组大鼠肾脏指数、空腹血糖(FBG)、血清肌酐(SCr)和血尿素氮(BUN)水平;通过HE和Masson染色观察肾脏形态学变化,并计算胶原容积分数(CVF);RT-qPCR检测肾脏组织中Klotho、TGF-β1和α-平滑肌肌动蛋白(α-SMA)的mRNA表达水平;Western blot检测肾脏组织中Klotho、TGF-β1、Smad3、磷酸化Smad3(p-Smad3)、α-SMA和结缔组织生长因子(CTGF)的蛋白水平。结果:对比其他各组,血流限制抗阻训练组大鼠FBG、SCr、BUN和肾脏CVF显著下降(P<0.05),Klotho表达水平显著上升(P<0.05),TGF-β1、p-Smad3、CTGF和α-SMA表达水平显著下降(P<0.05),Smad3表达水平无显著变化(P>0.05)。结论:血流限制抗阻训练可减轻T2DM大鼠肾纤维化程度,其机制可能与上调Klotho表达,阻断TGF-β1/Smad3信号通路,从而抑制细胞外基质的沉积有关。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 transforming growth factorβ1(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 creased(P<0.05),and the expression of TGF-β1,p-Smad3,CTGF andα-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 upregulation of Klotho expression,disruption of the TGF-β1/Smad3 signaling pathway,and inhibition of the deposition of epithelial-mesenchymal transformation.

关 键 词：2型糖尿病 肾纤维化 血流限制抗阻训练 KLOTHO TGF-β1/Smad3信号通路 

分 类 号：R587.1[医药卫生—内分泌] R363.2[医药卫生—内科学] R455[医药卫生—临床医学]