芪蛭降糖胶囊对糖尿病大鼠胰岛素抵抗的作用及其机制  

Effect of QizhiJiangtang Capsule on insulin resistance in diabetic rats and its mechanism

作　　者：张晓天[1] 陈禹[2] 于春江 袁语泽 郑敬彤[1] 张超[1] 赛景影[1] 宋晨雪[1] 谢婧书 王放[1] 

机构地区：[1]吉林大学基础医学院病原生物学教研室,吉林长春130021 [2]武警吉林省总队医院眼科,吉林长春130052 [3]吉林一正药业集团有限公司,吉林四平136001 [4]延边大学农学院植物系,吉林延吉133002

出　　处：《吉林大学学报（医学版）》2014年第4期805-811,共7页Journal of Jilin University：Medicine Edition

基　　金：吉林省科技厅"双十"工程重大科技成果转化项目资助课题(11ZDZH002)

摘　　要：目的:探讨芪蛭降糖胶囊(QJ)对糖尿病大鼠胰岛素抵抗(IR)的作用,阐明其药物作用的分子药理机制。方法:100只Wistar大鼠采用高脂饮食联合注射链脲佐菌素(STZ)的方法复制2型糖尿病大鼠模型。将建模成功大鼠随机分为模型组(DM),参芪降糖颗粒阳性对照组(SQ),芪蛭降糖胶囊低(QJL)、中(QJM)和高剂量组(QJH),同时设立正常对照组(NC)。芪蛭降糖胶囊低、中和高剂量组药物浓度分别为0.34、0.68和1.35g·kg-1;参芪降糖颗粒药物浓度为0.27g·kg-1。大鼠建模成功后,给予相应浓度药物干预治疗8周。经药物干预后,应用血糖检测仪及全自动生化分析仪测定大鼠空腹血糖(FBG)、空腹胰岛素(FINS)、胰岛素抵抗指数(IRI)和脂质代谢相关生化指标,Real Time PCR法测定肝脏组织中胰岛素受体底物1(IRS-1)、磷脂酰肌醇-3激酶(PI3K)和葡萄糖转运体4(GLUT4)基因的mRNA表达水平,ELISA法测定血清肿瘤坏死因子α(TNF-α)和脂联素(ADPN)水平。结果:与正常对照组比较,模型组大鼠FBG、FINS和IRI显著升高(P<0.05或P<0.01);血清总胆固醇(TC)、甘油三酯(TG)和低密度脂蛋白(LDL)水平显著升高(P<0.05),血清高密度脂蛋白(HDL)水平显著降低(P<0.05);肝脏组织中IRS-1、PI3K和GLUT4基因的mRNA表达水平显著下降(P<0.05),血清TNF-α水平显著升高(P<0.05),血清ADPN水平显著降低(P<0.05)。与模型组比较,芪蛭降糖胶囊低、中、高剂量组及参芪降糖颗粒阳性对照组大鼠FBG和IRI显著降低(P<0.01);芪蛭降糖胶囊中、高剂量组及参芪降糖颗粒阳性对照组FINS显著降低(P<0.05);芪蛭降糖胶囊中剂量组及参芪降糖颗粒阳性对照组血清TC、TG和LDL水平显著降低(P<0.05或P<0.01),HDL水平显著升高(P<0.05);肝脏组织中IRS-1、PI3K和GLUT4基因的mRNA表达水平显著上调(P<0.05);芪蛭降糖胶囊中、高剂量组及参芪降糖颗粒阳性对照组血清TNF-α水平显著降低(P<0.05),血清ADPN水平显著升高(P<0.05)。Objective To explore the effect of QizhiJiangtang Capsule on the insulin resistance（IR）in the diabetic rats,and to clarify the action mechanism.Methods The diabetes rat models were induced by high fat diet combined with STZ injection.The successful models of the rats were randomly divided into diabetes group（DM）,ShenqiJiangtang Granule group（SQ）and high（QJH）,middle-（QJM）,low（QJL）doses of QizhiJiangtang Capsule groups;at the same time control group（NC）was established.The drug concentrations in high,middle and low-doses of QizhiJiangtang Capsules groups were 1.35,0.68,and 0.34g·kg^-1 respectively;and the concentration of ShenqiJiangtang Granule was 0.27g·kg^-1.After the diabetic model was established successfully,the rats were treated for 8weeks on the basis of drug dose.Then the levels of fasting blood glucose（FBG）,fasting insulin（FINS）,insulin resistance index（IRI）and biochemical indexes related to lipid metabolism of the rats were measured using blood glucose detector and automatic biochemistry analyser.The gene expression of insulin receptor substrate-1（IRS-1）,phosphatidyl inositol 3-kinase（PI3K）,and glucose transporter 4（GLUT4）in liver tissue were examined by Real Time PCR.The levels of tumor necrosis factorα（TNF-α）and adiponectin（ADPN）in serum were detected using ELISA.Results Compared with control group,the levels of FBG,FINS and IRI of the rats in diabetes group were significantly increased（P〈0.05or P〈0.01）;the serum total cholesterol（TC）,triglyceride（TG）and low density lipoprotein（LDL）levels were significantly increased（P〈0.05）,while the serum high-density lipoprotein（HDL）level was significantly decreased（P〈0.05）;the mRNA expression levels of IRS-1,PI3Kand GLUT4in liver tissue were decreased（P〈0.05）;the level of serum TNF-αwas increased（P〈0.05）,but the ADPN level was decreased（P〈0.05）.Compared with diabetes group,the FBG level and IRI of the rats in QizhiJiangtang Capsule and ShenqiJiangta

关 键 词：芪蛭降糖胶囊 糖尿病 实验性 胰岛素抵抗 胰岛素受体底物1 磷脂酰肌醇-3激酶 葡萄糖转运体4 

分 类 号：R587.1[医药卫生—内分泌]