芪蛭降糖胶囊对糖尿病大鼠胰岛素抵抗的作用及其机制

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1.35 g·kg-1；参芪降糖颗粒药物浓度为0.27 g·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）。结论：芪蛭降糖胶囊具有改善糖尿病大鼠 IR的作用，其作用机制与改善糖脂代谢、影响胰岛素信号传导通路有关。%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 0.34 g · kg-1 respectively;and the concentration of ShenqiJiangtang Granule was 0.27 g·kg-1.After the diabetic model was established successfully, the rats were treated for 8 weeks 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<0.05 or 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,PI3K and GLUT4 in 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 ShenqiJiangtang Granule groups were significantly decreased (P<0.01);the levels of FINS of the rats middle and high doses of in QizhiJiangtang Capsule groups and ShenqiJiangtang Granule group were significantly decreased (P<0.05);the levels of serum TC,TG and LDL of the rats in middle dose of QizhiJiangtang Capsule group and ShenqiJiangtang Granule group were significantly decreased (P<0.05 or P<0.01),but the HDL level was increased (P<0.05);the mRBA expression lvels of IRS-1,PI3K and GLUT4 inliver tissue were increased (P<0.05);the levels of serum TNF-αof the rats in middle dose of QizhiJiangtang Capsule group and Shenqijiangtang Granule group were significantly decreased (P<0.05),but the serum ADPN levels were increased (P<0.05 ). Conclusion QizhiJiangtang Capsule can significantly improve the IR in the diabetic rats,and the pharmacological mechanisms are related to adapting the blood lipid component and insulin signal transduction pathways.