EGCG通过抑制TGF-β1/Smads信号通路改善高脂高糖饮食诱导的肥胖大鼠心肌纤维化

EGCG Improves Myocardial Fibrosis Induced by High Fat and High Sugar Diet in Obese Rats by Inhibiting TGF-β1/Smads Signaling Pathway

目的研究表没食子儿茶素没食子酸酯(epigallocatechin gallate,EGCG)对高脂高糖饮食诱导的肥胖大鼠心肌纤维化影响,探讨EGCG能否通过TGF-β1/Smads信号通路减轻心肌纤维化的程度。方法采用长期高脂高糖饮食形成肥胖大鼠模型,给予EGCG每天灌胃,治疗4周后,称取各组大鼠体重,Masson染色检测心肌纤维化的程度。生化检测血清中空腹血糖(FBG)、甘油三酯(TG)、总胆固醇(TC)、丙二醛(MDA)和谷胱甘肽(GSH)的含量。Western blotting检测各组大鼠心脏组织中相关蛋白(CollagenⅠ、CollagenⅢ、TGF-β1、Smad2/3、p-Smad2/3、Smad7)的表达水平。结果与正常组比较,模型组大鼠体重增加,给予EGCG治疗后减轻。与正常组比较,模型组大鼠心肌纤维化程度严重,给予EGCG治疗后减轻。与正常组比较,模型组大鼠FBG、TC、TG、MDA高于正常组,给予EGCG治疗后下降。与正常组比较,模型组大鼠GSH活性低于正常组,给予EGCG治疗后升高。与正常组比较,模型组大鼠CollagenⅠ、CollagenⅢ、TGF-β1、Smad2/3、pSmad2/3蛋白表达升高,给予EGCG治疗后下降。与正常组比较,模型组大鼠Smad7蛋白表达低于正常组,给予EGCG治疗后升高。结论EGCG能够改善肥胖大鼠血糖和脂质代谢紊乱,减轻心肌纤维化程度,其机制可能与氧化应激介导的TGF-β1/Smads信号通路有关。

Objective To investigate the effects of epigallocatechin gallate (EGCG) on myocardial fibrosis induced by high fat and high sugar diet in obese rats and to explore whether EGCG can reduce the extent of myocardial fibrosis through TGF-β1/Smads signaling pathway.Methods A obese rat model was formed by longterm high fat and high sugar diet.After 4 weeks of EGCG intragastric administration daily in obese rats,the body weight of every group rats was examined.The extent of myocardial fibrosis was detected by Masson staining.The contents of fasting blood glucose(FBG),triglyceride(TG),total cholesterol(TC),malondialdehyde(MDA) and glutathione(GSH) in serum were determined by biochemical methods.Western blotting was used to detect the expression levels of Collagen Ⅰ,Collagen Ⅲ,TGF-β1,Smad2/3,p-Smad2/3 and Smad7 in heart tissues of the rats in each group.Results The body weight of the model group rats was incremental than those in the control group and the body weight of EGCG treatment was lower.The extent of myocardial fibrosis was more severe in the model group to the control group,and decreased after EGCG treatment.The contents of FBG,TC,TG and MDA in model group were higher than those in the control group,but decreased after EGCG treatment.The activity of GSH in the model group was lower than that in the control group,but increased after EGCG treatment.Collagen Ⅰ,CollagenⅢ,TGF-β1,Smad2/3 and p-Smad2/3 were increased in the model group,but decreased after EGCG treatment.Smad7 protein expression in the model group was lower than that in the control group,but increased after EGCG treatment.Conclusion EGCG can improve the lipid metabolism disorder and reduce MF degree in obese rats,which can be related to TGF-β1/Smads signaling pathway mediated by oxidative stress.