积雪草醇提物对2型糖尿病ZDF大鼠肝脏胰岛素抵抗的影响

Effect of Centella Asiatica Alcohol Extract on Hepatic Insulin Resistance of Zucker Fatty Diabetes Rats

目的:探讨积雪草醇提物对2型糖尿病(type 2 diabetes mellitus,T2DM)ZDF(Zucker diabetic fatty)大鼠肝脏胰岛素抵抗的作用机制。方法:6只雄性ZDF(fa/+)大鼠设为正常组,成模的雄性ZDF(fa/fa)大鼠18只根据体重及随机血糖分层随机分为3组,模型组(生理盐水10 m L·kg^(-1)),二甲双胍(二甲双胍片0.18 g·kg^(-1)·d^(-1))组,积雪草(积雪草醇提物0.1 g·kg^(-1)·d^(-1))组。每2周监测大鼠体重,随机血糖(random blood glucose,RBG),空腹血糖(fasting blood glucose,FBG);给药6周后取材,检测大鼠空腹血糖及空腹血清胰岛素(fasting serum insulin,FINS),并计算胰岛素抵抗指数(homeostasis model of assessment for insulin resistence index,HOMA-IR)。采用实时荧光定量聚合酶链式反应(Real-time polymerase chain reaction,Real-time PCR)法检测各组大鼠肝脏组织中胰岛素受体2(insulin receptor substrate 2,IRS2),3-磷酸肌醇依赖性蛋白激酶1(3-phosphoinositide-dependent protein kinase1,PDK1)及葡萄糖转运蛋白2(glucose transporter 2,GLUT2)mRNA的表达情况;免疫组化法观察肝脏中PDK1,IRS2蛋白表达情况。结果:与模型组比较,积雪草组及二甲双胍组均可显著改善ZDF大鼠体重,RBG,FBG水平及HOMA-IR(P<0.01);积雪草组IRS2,PDK1及GLUT2 mRNA相对表达量及PDK1,IRS2蛋白表达水平显著增加(P<0.01)。结论:积雪草醇提物能有效改善2型糖尿病ZDF大鼠肝脏胰岛素抵抗,其作用机制可能与胰岛素信号传导通路中IRS2,PDK1的表达及葡萄糖转运中GLUT2的表达相关。

Objective： To investigate the mechanism of centella asiatica alcohol extract on hepatic insulin resistance of Zucker diabetes fatty（ZDF） rats. Method： Six male（fa/＋） ZDF rats were selected as control group,and 18 modeled male（fa/fa） ZDF rats were randomly divided into three groups,namely model group（normal saline 10 ml·kg-1）,metformin group（0. 18 g·kg-1·d-1） and centella asiatica group（0. 1 g·kg-1·d-1）based on body weight and random blood glucose. Body weight,random blood glucose and fasting blood glucose were monitored every two weeks. Materials were collected six weeks later to measure the fasting blood glucose（FBG） and fasting serum insulin,and calculate insulin resistance index homeostasis model of assessment for insulin resistance index（HOMA-IR）. Gene expressions of insulin receptor substrate 2（IRS2）, 3-phosphoinositide-dependent protein kinase 1（PDK1） and glucose transporter 2（GLUT2） in the liver were detected by Real-time polymerase chain reaction（Real-time PCR）. Protein expressions of PDK1 and IRS2 were observed by immuno-histochemical method. Result： The administration groups could significantly improve weight,random blood glucose,fasting blood glucose,fasting serum insulin and insulin resistance index of（fa/fa） ZDF rats（P〈0.01）. Compared with model group,IRS2,PDK1 and GLUT2 mRNA expressions and PDK1 and IRS2 protein expressions of centella asiatica group increased（P〈0.01）. Conclusion： Centella asiatica alcohol extract can effectively improve the hepatic insulin resistance of（fa/fa） ZDF rats. Its mechanism may be related to expressions of IRS2,PDK1 in insulin signaling pathway and glucose transporter GLUT2.