黄芪总苷对实验性糖尿病小鼠心肌保护作用的研究

摘要

目的 探讨黄芪总苷(AST)对链脲霉素(STZ)诱导实验性糖尿病(DM)小鼠心肌的保护作用以及其可能作用机制.方法 STZ(100 mg/kg)一次性腹腔注射建立DM小鼠模型,随机分为正常组,模型组,AST(30、60、120 mg/kg)组及四甲基哌啶(90 mg/kg)组.6周后检测各组小鼠体重、心脏指数、血糖浓度、血清超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性和丙二醛(MDA)含量的变化,HE染色观察心肌组织病理形态学变化,TUNEL法观察心肌细胞凋亡情况,免疫组化法、RT-PCR法观察心肌组织中转化生长因子(TGF-β1)的表达情况.结果 与正常组比较,模型组小鼠血糖、心脏指数明显升高,血清SOD和GSH-Px活性降低,MDA含量升高,心肌纤维紊乱,心肌细胞凋亡增加,心肌组织中TGF-β1和TGF-β1 mRNA表达增加.与模型组比较,AST(30、60、120 mg/kg)组明显降低DM小鼠血糖、心脏指数;提高DM小鼠血清SOD和GSH-Px活性,降低MDA含量;改善心肌纤维、心肌细胞异常;降低心肌组织中TGF-β1的表达.结论 AST能抑制DM小鼠心肌纤维化病变以及心肌细胞凋亡,对DM小鼠心肌起保护作用,其作用机制可能与其提高血清抗氧化能力、降低心肌组织中TGF-β1的表达水平有关.%To study the effect of Astragalosides ( AST ) on myocardial damage and the mechanism in diabetic mice induced by Streptozotocin ( STZ ). Methods The diabetic mice model was made by single intraperito-neal injection of STZ (100 mg/kg ). Then the mice were randomly divided into control group,diabetic model group, AST ( 30,60,120 mg/kg ) and Tempol ( 90 mg/kg ) treated groups. After 6 weeks of treatment,the body weight, heart index, blood glucose and serum SOD, GSH-Px activity and MDA content were measured. HE staining was used to observe myocardial histopathology, and TUNEL was used to measure the myocardial apoptosis. The immunohisto-chemistry and RT-PCR were used to detect the expression of TGF-β1. Results Compared with control group, the blood glucose, heart index, myocardial damage and apoptosis increased significantly in diabetic model group, and the expression of TGF-β1 was increased in model mice. Compared with model group, AST ( 30,60,120 mg/kg) treatment could decrease blood glucose, increase serum SOD and GSH-Px activities and decrease MDA content. AST (30,60,120 mg/kg ) could improve the myocardial histopathological changes and decrease myocardial apoptosis and TGF-β1 expression. Conclusion AST can inhibit myocardial fibrosis and apoptosis in diabetics mice. It may be related to increase the antioxidant activity and reduce the expression of TGF-β1.