【摘要】 目的:研究高脂加链脲佐菌素(STZ)诱导的糖尿病心肌病大鼠心肌组织中解偶联蛋白2(UCP2)与腺苷酸活化蛋白激酶(AMPK)的表达变化,并探讨黄芪多糖(APS)的治疗作用及可能机制。方法:雄性SPF级SD大鼠随机分为:正常对照组(C组,n=8),黄芪多糖对照组(C+APS组,n=8),饲以正常饲料;通过高脂饮食+小剂量STZ(25 mg/kg,尾静脉注射)复制2型糖尿病大鼠模型,将血糖>13.9 mmol/L者随机分为糖尿病组(DM组,n=8)及黄芪多糖治疗组(DM+APS组,n=8);DM+APS组行黄芪多糖灌胃治疗8周[700 mg/(kg.d)]。进行口服葡萄糖耐量(OGTT)试验,检测动物血糖、血浆胰岛素,并计算胰岛素敏感指数(ISI);取心室肌组织提取蛋白,Western blot-ting检测UCP2、总AMPK和pAMPKα1的表达。结果:DM组出现高血糖、糖耐量降低、低胰岛素敏感性等2型糖尿病特征;DM+APS组UCP2水平较DM组明显增高,伴随pAMPK表达增高(P<0.05),而在C与C+APS组两种结果无明显差异。结论:APS治疗可以显著改善2型糖尿病大鼠胰岛素抵抗,主要表现为降低血糖、升高ISI指数,其作用机制可能与增强AMPK活性,增加UCP2表达,改善2型糖尿病大鼠能量代谢等途径有关。更多还原

【Abstract】 Objective: To investigate the expression of uncoupling protein 2(UCP2) and activation of AMP-activated protein kinase(AMPK) in myocardium of type 2 diabetic rats which were induced by high fat diet and streptozotocin(STZ),and to explore the treatment of astragalus polysaccharide(APS).Methods: Male SD rats were randomly divided into four groups: control group(C,n=8),APS control group(C+APS,n=8),which were fed with normal food,diabetes mellitus group(DM,n=8),and APS treated group(DM+APS,n=8),which were established by high fat diet and STZ injection at small dosage(25 mg/kg).Group DM+APS and C+APS were treated with 700 mg/(kg·d) APS for 8 weeks.Blood glucose,oral glucose tolerance test(OGTT),plasma insulin concentration and insulin sensitivity index were periodically tested.At the end of 8-week treatment with APS,the expression of UCP2,the total AMPK,and the pAMPK(Thr172) in the myocardium were assayed by Western blotting.Methods: After being treated with APS for 8 weeks,the index of FBG and OGTT in group DM+APS markedly decreased comparing with those of group DM(both P<0.05).There was a significant increasing of the expression of UCP2 in group DM+APS compared with that in group DM(P<0.05),and the phosphorylation AMPK in DM+APS was higher than in group DM.There were no obvious changes both in UCP and in AMPK in group C and C+APS.Conclusion: After treatment with APS for 8 weeks,there is a significant decrease of blood glucose,and an increase of insulin sensitivity in diabetic rats.The potential mechanisms of therapeutic effect of APS on diabetic cardiomyopathy rats may involve in the following pathways: decreasing the level of FBG and oral glucose tolerance,increasing ISI,attenuating cardiac hypertrophy,promoting the phosphorylation of AMPK,and increasing the expression of UCP2 in myocardium of rats.更多还原