黄芪多糖对非酒精性脂肪性肝炎大鼠ACE2-[Ang-(1-7)]-Mas轴及胰岛素抵抗的影响

目的探讨黄芪多糖对非酒精性脂肪性肝炎大鼠ACE2-Ang-(1-7)]-Mas轴及胰岛素抵抗的影响。方法 40只大鼠随机分为正常组、模型组、黄芪多糖组(400 mg/kg)、吡格列酮组(20 mg/kg),每组10只,高脂饲料建立非酒精性脂肪性肝炎大鼠模型。给药4周后,测定体质量、肝湿重、血脂、肝功能、血清Ang(1-7)水平,观察肝脏组织病理学变化,RT-PCR、Western blot检测肝组织ACE2、Mas、IRS-1水平。结果与模型组比较,黄芪多糖组肝指数及ALT、AST、TG、TC、MDA水平显著降低(P<0.01),Ang-(1-7)、SOD水平,Mas、ACE2、IRS-1 mRNA及蛋白表达显著升高(P<0.05,P<0.01),肝脂肪变性、炎症反应明显减轻。结论黄芪多糖可有效缓解非酒精性脂肪性肝炎大鼠胰岛素抵抗,其机制可能与上调ACE2-Ang-(1-7)]-Mas轴基因表达、改善胰岛素敏感性有关。

Effects of Astragali Radix polysaccharides on ACE2-[Ang-(1-7)]-Mas axis and insulin resistance in non-alcoholic steatohepatitis rats

AIM To explore the effects of Astragali Radix polysaccharides on ACE2-Ang-(1-7)]-Mas axis and insulin resistance in non-alcoholic steatohepatitis rats.METHODS Forty rats were randomly divided into normal group,model group,Astragali Radix polysaccharides group(400 mg/kg)and pioglitazone group(20 mg/kg),10 rats in each group.The rat model for non-alcoholic steatohepatitis was established by high-fat diet.After 4-week administration,body weight,liver wet weight,serum lipid,liver function and serum Ang(1-7)level were detected and liver histopathological changes were observed.ACE2,Mas and IRS-1 levels in liver tissue were detected by RT-PCR and Western blot.RESULTS Compared with the model group,the Astragali Radix polysaccharides group demonstrated significant decrease in liver index and ALT,AST,TG,TC,MDA levels(P<0.01),marked increase in Ang-(1-7),SOD levels and Mas,ACE2,IRS-1 mRNA,protein expressions(P<0.05,P<0.01),as well as obvious reduction in liver fatty degeneration and inflammatory reactions.CONCLUSION Astragali Radix polysaccharides can effectively alleviate insulin resistance in non-alcoholic steatohepatitis rats,whose mechanisms may contribute to the up-regulation of ACE2-Ang-(1-7)]-Mas axis gene expression and improvement of insulin sensitivity.