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

摘要：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？rd)]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。
ABSTRACT: 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 [400mg/(kg？d)] solution. CQ group was intragastrically administered with CQ solution [50mg/(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 to β-catenin/TCF4/GSK-3β and 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/Ⅰ ratio 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 of β-catenin, TCF4 and MYC were significantly improved in DM group as compared with NG group (P<0.05), and there were higher p-GSK3β/GSK3β and p-MTOR/MTOR ratios in DM group (P<0.05). GTP treatment significantly decreased the protein expressions of β-catenin, TCF4 and MYC, and also decreased p-GSK3β/GSK3β and p-MTOR/MTOR ratios compared with DM group (P<0.05). Conclusion GTP participates in the protection of heart function in DCM rats by regulating β-catenin/TCF4/GSK-3β and MTOR pathways related to autophagy