黄芪多糖对糖尿病心肌病大鼠自噬的调控机制研究

Regulation mechanism of Astragalus Polysaccharides by autophagy on Diabetic Cardiomyopathy rats

目的研究黄芪多糖(APS)对糖尿病心肌病(DCM)大鼠的自噬干预作用。方法80只健康雄性SD大鼠随机选取10只作为空白对照组(Control组),余下70只采用高糖高脂饮食联合STZ腹腔注射复制DCM模型。将模型复制成功的大鼠随机分为模型对照组(DCM组)、黄芪多糖组(APS组)、氯喹组(CQ组)、黄芪多糖+氯喹组(APS+CQ组)。APS组灌服APS溶液(800mg/kg),CQ组皮下注射CQ(25mg/kg),APS+CQ组同时给予APS溶液和CQ,模型组和空白组均灌胃等容积生理盐水。8周后,透射电镜观察心肌超微结构的改变,血糖仪检测尾静脉血糖,生化仪分析大鼠血清HbA1c、TG、TC、HDL-C、LDL-C的水平,Western blot检测大鼠心肌组织Beclin-1、LC3II/I的蛋白表达水平,Real-time PCR检测心肌组织Beclin-1、LC3II mRNA的表达情况。结果与Control组比较,DCM组大鼠FBG、HbA1c、TG、TC、LDL-C明显升高,LC3II/I蛋白、Beclin-1蛋白、Beclin 1 mRNA、LC3II mRNA明显降低(P<0.05)。与DCM组比较,APS组FBG、HbA1c、TG、TC、LDL-C蛋白明显降低,LC3II/I、Beclin-1蛋白、Beclin-1 mRNA、LC3II mRNA明显升高(P<0.05)。与APS组比较,APS+CQ组大鼠心肌LC3II/I、Beclin-1、LC3II mRNA水平明显降低,FBG、HbA1c、TG、TC、LDL-C水平明显升高(P<0.05)。结论APS能调节自噬,进而发挥对DCM的保护作用。

Objective To observe the effect of Astragalus Polysaccharides(APS)on autophagy in diabetic cardiomyopathy(DCM)rats.Methods 80 healthy male SD rats were randomly selected as control group(10 rats),and the remaining 70 rats were treated with high sugar and high fat diet combined with STZ intraperitoneal injection to establish DCM model.The model rats were randomly divided into model control group(DCM group),astragalus polysaccharide group(APS group),chloroquine group(CQ group),astragalus polysaccharide+chloroquine group(APS+CQ group).APS group was given APS solution(800 mg/kg),CQ group was given CQ(25 mg/kg),APS+CQ group was given APS solution and CQ at the same time,model group and control group were given equal volume of normal saline.After 8 weeks,the ultrastructural changes of myocardium were observed by transmission electron microscope,the tail vein blood glucose was detected by blood glucose meter,the serum levels of HbA1 c,TG,TC,HDL-C and LDL-C were analyzed by biochemical analyzer,the protein expression levels of beclin-1 and LC3 II/I in myocardium were detected by Western blot,and the mRNA expression levels of beclin-1 and LC3 II in myocardium were detected by real-time PCR.Results Compared to the control group,FBG,HbA1 c,TG,TC and LDL-C in DCM group were significantly increased,while LC3 II/I protein,beclin-1 protein,Beclin 1 mRNA and LC3 II mRNA were significantly decreased(P<0.05).Compared to the DCM group,the protein levels of FBG,HbA1 c,TG,TC and LDL-C in APS group were significantly decreased,while LC3 II/I,beclin-1 protein,beclin-1 mRNA and LC3 II mRNA were significantly increased(P<0.05).Compared to the APS group,the mRNA levels of LC3 II/I,beclin-1 and LC3 II in APS+CQ group were significantly decreased,and the levels of FBG,HbA1 c,TG,TC and LDL-C were significantly increased(P<0.05).Conclusion APS can regulate autophagy and protect DCM.