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。
Objective 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 intraperitoneal 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 immunohistochemistry 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.