茶多酚对糖尿病心肌病大鼠心功能的保护作用及其机制

The protective effect of teapolyphenol on cardiac function in diabetic cardiomyopathy rats and its mechanism

目的观察茶多酚(green tea polyphenol,GTP)保护糖尿病心肌病(diabetic cardiomyopathy,DCM)大鼠心功能的作用机制。方法建立链脲佐菌素诱导的1型糖尿病大鼠并随机分为正常对照组(NG,n=15)、糖尿病组(DM,n=12)、GTP组(n=12)、GTP+氯喹(CQ)组(n=11)、CQ组(n=12)。NG组和DM组灌胃蒸馏水,GTP组灌胃GTP[400mg/(kgd)]溶液,CQ组灌胃CQ溶液(50mg/kg),GTP+CQ组灌胃等量的CQ和GTP溶液。Western blot检测左心室心肌组织中β-catenin/TCF4/GSK-3β和MTOR通路相关蛋白的表达。结果与NG组相比,DM组中LC3-Ⅱ/Ⅰ比值和BECN1表达显著降低(P<0.05),且SQSTM1水平显著增加(P<0.05)。与DM组相比,GTP组LC3-Ⅱ/Ⅰ比值和BECN1蛋白表达水平显著增加(P<0.05),同时SQSTM1蛋白水平显著降低(P<0.05)。与NG组相比,DM组β-catenin、TCF4和MYC的蛋白表达均显著提高(P<0.05),且p-GSK3β/GSK3β和p-MTOR/MTOR的比值显著提高(P<0.05)。与DM组相比,GTP组的β-catenin、TCF4和MYC蛋白表达水平及p-GSK3β/GSK3β和p-MTOR/MTOR的比值显著降低(P<0.05)。结论 GTP可以通过调节与自噬相关的β-catenin/TCF4/GSK-3β和MTOR通路参与对DCM大鼠的心功能保护作用。

Objective To investigate the protective effect of green tea polyphenol(GTP)on cardiac function in diabetic cardiomyopathy(DCM)rats and its mechanism.Methods After the model of type 1 diabetes was established by streptozotocin induction in rats,they were randomly divided into the following 5 groups for treatment:NG group(n=15),DM group(n=12),GTP group(n=12),GTP+CQ group(n=11),and CQ group(n=12).NG and DM groups were given gastric lavage of distilled water.GTP group was intragastrically administered with GTP[400 mg/(kg·d)]solution.CQ group was intragastrically administered with CQ solution[50 mg/(kg·d)].GTP+CQ group was intragastrically administered with CQ and GTP solution of the same volume.Western blot was used to detect the expression of protein related toβ-catenin/TCF4/GSK-3βand MTOR pathways in the left ventricular myocardium.Results Compared with those in NG group,the LC3-Ⅱ/Ⅰ/ratio and BECN1 expression were significantly decreased(P<0.05)while SQSTM1 level was significantly increased(P<0.05)in DM group.The LC3-Ⅱ/Ⅰratio and BECN1 protein expression level were higher in GTP group than in DM group(P<0.05),while SQSTM1 protein expression level was lower(P<0.05).The protein expressions ofβ-catenin,TCF4 and MYC were significantly improved in DM group as compared with NG group(P<0.05),and there were higher p-GSK3β/GSK3βand p-MTOR/MTOR ratios in DM group(P<0.05).GTP treatment significantly decreased the protein expressions ofβ-catenin,TCF4 and MYC,and also decreased p-GSK3β/GSK3βand p-MTOR/MTOR ratios compared with DM group(P<0.05).Conclusion GTP participates in the protection of heart function in DCM rats by regulatingβ-catenin/TCF4/GSK-3βand MTOR pathways related to autophagy.