表没食子儿茶素没食子酸酯对糖尿病大鼠心脏的保护作用及对TGF-β1/Smad3信号通路表达的影响

摘要

Objective To investigate the effects of Epigallocatechin gallate (EGCG) on cardiac protection in diabetic rats and the expression of TGF-1/Smad3 signaling pathway. Methods The influence of clean level 40 SD rats, weight 200-220 g, divided into four random groups:control (Sham) group, diabetic cardiomyopathy model (DC) group, EGCG group, and metformin positive control group (Met).Post 8 weeks of high-fat-diet administration, the rats were injected intraperitoneally with STZ to establish the diabetes cardiomyopathy model. Upon successful model establishment, the EGCG group was intraperitoneally injected with EGCG and the cardiac function of the rats was measured after 28 days of drug administration. Then, the pathological results of the myocardial tissue were analyzed. Triglyceride (TG), total cholesterol (TC), glycosylated hemoglobin (HbA1 c), and blood glucose (FBG) concentrations were also measured. Further, the concentrations of superoxide dismutases (SOD), malondialdehyde (MDA), catalase (CAT), and glutathione peroxidase (GPX) in serum were measured by ELISA. The expression of TGF-β1 and Smad3 in kidney tissues of the rats was measured by Western blotting analysis. Results EGCG could reduce the glucose, lipid, and MDA levels in the blood of the diabetic rats, enhance cardiac systolic and diastolic functions, inhibit TGF-β1 and Smad3 protein expression, enhance the activity of SOD, CAT and GPX, and reduce myocardial tissue fibrosis. Conclusion EGCG can protect diabetic rat hearts by improving metabolic disorder, and its mechanism may be related to the oxidative-stress mediated by the TGF-β1/Smad3 signaling pathway.%目的 探讨表没食子儿茶素没食子酸酯(EGCG)对糖尿病大鼠的心脏保护作用及对TGF-β1/Smad3信号通路表达的影响.方法 清洁级SD大鼠40只,体质量200～220 g,随机分为4组:假手术组(Sham组)、2型糖尿病心肌病模型组(DC组)、EGCG组和二甲双胍阳性对照组(Met组),大鼠饲喂高脂饲料8周后,腹腔注射STZ建立2型糖尿病心肌病模型.EGCG组于造模成功后腹腔注射EGCG,于给药28 d后生理记录仪检测各组大鼠心脏功能;观察大鼠心肌组织病理学结果;生化检测甘油三酯(TG)、总胆固醇(TC)、糖化血红蛋白和空腹血糖浓度;ELISA检测血清中超氧化物歧化酶(SOD)、丙二醛(MDA)、过氧化氢酶(CAT)和谷胱甘肽过氧化酶(GPX)的含量;Western blotting法检测各组大鼠心脏组织中TGF-β1、Smad3蛋白表达.结果 EGCG可以降低糖尿病大鼠血糖、血脂和MDA的表达,增强心脏收缩和舒张功能,抑制TGF-β1、Smad3蛋白表达,提升SOD、CAT和GPX的活性,减轻心肌组织的纤维化.结论 EGCG可通过改善代谢紊乱对糖尿病大鼠心脏实现保护作用,其机制可能与TGF-β1/Smad3信号通路介导的氧化应激有关.