黄芪多糖介导NRG-1/ErbB信号通路对糖尿病心肌细胞凋亡的作用

Astragalus polysaccharide reduces myocardial tissue apoptosis through NRG-1/ErbB signal pathway in rats

目的:从NRG-1/Erb B信号通路探讨黄芪多糖对糖尿病心肌病大鼠心肌细胞凋亡的影响。方法:雄性SD大鼠给予高糖高脂饮食4周后用负荷小剂量的STZ诱导糖尿病大鼠模型,另设正常组。将造模成功的大鼠按随机数字表法分为模型组、黄芪低剂量组、黄芪高剂量组和二甲双胍组。黄芪低剂量组和高剂量组分别给予400 mg·kg^(-1)·d^(-1)、800 mg·kg^(-1)·d^(-1)处理,二甲双胍组给予160 mg·kg^(-1)·d^(-1)处理,给药结束后分别测定空腹血糖、胰岛素、甘油三酯、总胆固醇含量,并进行超声心动图检测、心肌组织HE染色和TUNEL染色分析及Western blot分析Erb B2、AKT、Bax、Bcl-2表达水平。结果:与对照组比较,模型组空腹血糖、总胆固醇、甘油三酯含量明显升高,血胰岛素水平显著降低,心肌功能受损,心肌细胞排列紊乱,细胞肥大变形,细胞核深染,间质纤维化明显,心肌组织凋亡增加。Erb B2、AKT、Bcl-2表达显著降低,Bax表达显著增加;与模型组比较,黄芪高剂量组和二甲双胍组空腹血糖、总胆固醇、甘油三酯含量显著降低,血胰岛素水平显著升高,心肌功能一定程度上得以恢复,肌细胞肥大变形有所改善,间质纤维化得到明显改善,心肌组织凋亡也显著降低。Erb B2、AKT、Bcl-2表达显著增加,Bax表达显著降低。结论:高剂量组的黄芪多糖可减轻糖尿病心肌病大鼠的血糖、胆固醇及甘油三酯,减少心肌细胞凋亡,改善心功能,其作用机制可能与NRG-1/Erb B信号通路有关。

Objective： To examine the potential effect of Astragalus polysaccharide（ APS） on diabetic cardiomyopathy in rats. Method： Male SD rats fed a high-glucose and hyper-lipid diet for 4 weeks. Then diabetes mellitus model was induced by a single injection of STZ. Diabetes SD rats were randomly divided into model group,low-dose APS group,highdose APS group and metformin group. Low-dose APS group,high-dose APS group and metformin group were treated with400 mg·kg^（-1）·d^（-1）,800 mg·kg^（-1）·d^（-1）of APS,and 160 mg·kg^（-1）·d^（-1）of metformin respectively. Another 12 rats were assigned to the control group and received nothing treatment. After 12 weeks,the levels of fasting glucose,insulin in serum,triglyceride and total cholesterol were measured. Furthermore, the（ HE） staining and TUNEL staining of myocardial tissue was conducted. In addition,the expression level of Erb B2,AKT,Bax and Bcl-2 were performed using western blotting methods. Result： Compared to the control group,the levels of fasting glucose,triglyceride and total cholesterol increased significantly,and insulin in serum decreased dramaticly in model group. In contrast,the levels of fasting glucose,triglyceride and total cholesterol decreased,and the level of insulin in serum increased in high-dose APS group and metformin group. Moreover,myocardial tissue apoptosis increased markedly in model group,and decreased significantly in high-dose APS group and metformin group. In addition,the expression level of Erb B2,AKT,Bcl-2 were up-regulated significantly,and Bax expression was down-regulated significantly in model group. However,high dose of APS and metformin could reverse this situation： increased Erb B2,AKT,Bcl-2 expression and decreased Bax expression.Conclusion： High dose of APS had a beneficial effect on heart function by decreasing the level of glucose and lipid and relieving the heart damage in diabetic cardiomyopathy in rat,the mechanism might related to NRG-1/Erb B signal pathway.