论文部分内容阅读
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 alcohol extract of Centella asiatica on hepatic insulin resistance in type 2 diabetes mellitus (ZDM) diabetic ZDF rats. Methods: Six male ZDF (fa / +) rats were set as normal group. 18 male ZDF (fa / fa) rats were randomly divided into 3 groups according to body weight and random blood glucose level. (10 m L · kg -1), metformin (0.18 g · kg -1 · d -1) and Centella asiatica (0.1 g · kg -1) (-1) · d ~ (-1)) group. The body weight, random blood glucose (RBG) and fasting blood glucose (FBG) were monitored every 2 weeks. After 6 weeks’ administration, the fasting blood glucose and fasting serum insulin ), And calculate homeostasis model of assessment for insulin resistence index (HOMA-IR). Real-time polymerase chain reaction (Real-time PCR) was used to detect the expression of insulin receptor substrate 2 (IRS2), 3-phosphoinositide dependent (PDK1) and glucose transporter 2 (GLUT2) mRNA were detected by immunohistochemical method. The expression of PDK1 and IRS2 protein in liver were observed by immunohistochemistry. Results: Compared with model group, the body weight, RBG, FBG and HOMA-IR of ZDF rats (P <0.01) were significantly improved in the group of Centella asiatica and Metformin. The relative expression of IRS2, PDK1 and GLUT2 mRNA And PDK1, IRS2 protein expression increased significantly (P <0.01). CONCLUSION: Alcohol extract of Centella asiatica can effectively improve hepatic insulin resistance in type 2 diabetic ZDF rats. Its mechanism may be related to the expression of IRS2 and PDK1 in insulin signal transduction pathway and the expression of GLUT2 in glucose transport.