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

作　　者：吴莉娟[1] 孙文[2] 吴丽丽[2] 高健[3] 穆晓红[4] 秦灵灵[5] 刘铜华[5] WU Li-juan SUN Wen WU Li-li GAO Jian MU Xiao-hong QIN Ling-ling LIU Tong-hua(School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu 610072, China Health Cultivation Research Institution, Beijing University of Chinese Medicine, Beijing 100029, China Information Institute, University of International Business and Economics, Beijing 100029, China Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing 100700, China Beijing University of Chinese Medicine, Beijing 100029, China)

机构地区：[1]成都中医药大学临床医学院,成都610072 [2]北京中医药大学中医养生所,北京100029 [3]对外经济贸易大学信息学院,北京100029 [4]北京中医药大学东直门医院,北京100700 [5]北京中医药大学,北京100029

出　　处：《中国实验方剂学杂志》2017年第10期104-110,共7页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家国际科技合作专项(2012DFG31550)

摘　　要：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.

关 键 词：积雪草醇提物 2型糖尿病 ZDF大鼠 肝脏 胰岛素抵抗 

分 类 号：R285.5[医药卫生—中药学]