文献类型：期刊文献

中文题名：加味葛根芩连汤对糖尿病db/db小鼠内质网应激及胰岛素抵抗的影响

英文题名：Effects of Modified Gegen Qinlian Decoction on Endoplasmic Reticulum Stress and Insulin Resistance in Diabetes Mellitus db/db Mice

作者：王佳慧[1];柳荣[1];郝民琦[1];朱向东[2];梁永林[1]

第一作者：王佳慧

机构：[1]甘肃中医药大学基础医学院,甘肃兰州730000;[2]宁夏医科大学中医学院,宁夏银川750004

第一机构：甘肃中医药大学基础医学院（敦煌医学研究所）

年份：2023

卷号：30

期号：6

起止页码：123

中文期刊名：中国中医药信息杂志

外文期刊名：Chinese Journal of Information on Traditional Chinese Medicine

收录：CSTPCD;;CSCD:【CSCD_E2023_2024】；

基金：甘肃省教育厅产业支撑计划项目(2021CYZC-03);宁夏回族自治区重点研发计划(2022CMG02034);甘肃省优秀研究生“创新之星”项目(2022CXZX-734)。

语种：中文

中文关键词：2型糖尿病;加味葛根芩连汤;内质网应激;胰岛素抵抗;IRE1/JNK/IRS1信号通路;db/db小鼠

外文关键词：type 2 diabetes mellitus;Gegen Qinlian Decoction;endoplasmic reticulum stress;insulin resistance;IRE1/JNK/IRS1 signaling pathway;db/db mice

摘要：目的观察加味葛根芩连汤对糖尿病小鼠肝脏内质网应激及胰岛素抵抗的影响,探讨其改善2型糖尿病的作用机制。方法将65只db/db小鼠随机分为模型组、二甲双胍组和加味葛根芩连汤低、中、高剂量组,每组13只,另取13只m/m小鼠作为空白组,给药组分别予相应药物灌胃12周。检测小鼠体质量、空腹血糖(FBG)、糖化血红蛋白(HbA1c),ELISA检测血清空腹胰岛素(FINS)、游离脂肪酸(FFA)水平,全自动生化分析仪检测血清总胆固醇(TC)、三酰甘油(TG)含量,HE染色观察肝组织病理改变,油红O染色观察肝脏脂质蓄积,Western blot检测肝组织肌醇需求酶1(IRE1)、p-IRE1、c-Jun氨基末端激酶(JNK)、p-JNK、胰岛素受体底物1(IRS1)、p-IRS1蛋白表达,RT-PCR检测肝组织IRE1、JNK、IRS1 mRNA表达。结果与空白组比较,模型组小鼠体质量、FBG、FINS、HbA1c、FFA、TC、TG水平均显著升高,肝组织结构严重破坏,组织内有大量脂滴,肝组织IRE1、p-IRE1、JNK、p-JNK蛋白表达显著升高,IRS1、p-IRS1蛋白表达显著降低,IRE1、JNK mRNA表达显著升高,IRS1 mRNA表达显著降低,差异均有统计学意义(P<0.01);与模型组比较,加味葛根芩连汤高剂量组和二甲双胍组小鼠体质量、FBG、FINS、HbA1c、FFA、TC、TG水平显著降低,肝组织损伤有所减轻,肝细胞脂质蓄积减少,肝组织IRE1、p-IRE1、JNK、p-JNK蛋白表达显著降低,IRS1、p-IRS1蛋白表达显著升高,IRE1、JNK mRNA表达显著降低,IRS1 mRNA表达显著升高,差异均有统计学意义(P<0.05,P<0.01)。结论加味葛根芩连汤可能通过调节IRE1/JNK/IRS1信号通路抑制胰岛素抵抗,减轻内质网负荷,对2型糖尿病起治疗作用。
Objective To observe the effects of modified Gegen Qinlian Decoction on endoplasmic reticulum stress and insulin resistance in liver of db/db mice;To explore its mechanism of improving type 2 diabetes mellitus.Methods Totally 65 db/db mice were randomly divided into model group,metformin group and modified Gegen Qinlian Decoction low-,medium-and high-dosage groups,with 13 mice in each group.Another 13 m/m mice were selected as the blank group,and the medication groups were given corresponding drugs by gavage for 12 weeks.The body mass,FBG and HbA1c of mice were measured;the levels of FINS,FFA were detected by ELISA;automatic biochemical analyzer was used to detected serum TC and TG;the pathological changes of liver were observed by HE staining;the lipid accumulation in liver was observed by oil red O staining;Western blot was used to detect the protein expressions of inositol requiring enzyme 1(IRE1),p-IRE1,c-Jun N-terminal kinase(JNK),p-JNK,insulin receptor substrate 1(IRS1)and p-IRS1 in liver tissue;the mRNA expressions of IRE1,JNK and IRS1 in liver tissue were detected by RT-PCR.Results Compared with the blank group,the body mass,FBG,FINS,HbA1c,FFA,TC and TG levels of the mice in model group significantly increased,with severe destruction of liver tissue structure,there were a lot of lipid droplets in the tissue,and the expressions of IRE1,p-IRE1,JNK,p-JNK protein in liver tissue significantly increased,the expressions of IRS1 and p-IRS1 protein significantly decreased,the expressions of IRE1 and JNK mRNA significantly increased,the expression of IRS1 mRNA significantly decreased,with statistical significance(P<0.01).Compared with the model group,the body mass,FBG,FINS,HbA1c,FFA,TC and TG levels in the modified Gegen Qinlian Decoction high-dosage group and metformin group decreased significantly,the damage of liver tissue was eased,and the lipid accumulation of liver cells reduced,the expressions of IRE1,p-IRE1,JNK,p-JNK protein in liver tissue significantly decreased,the expressions of IRS1 and p-IRS1 protein significantly increased,while the expressions of IRE1 and JNK mRNA significantly decreased,the expression of IRS1 mRNA significantly increased,with statistical significance(P<0.05,P<0.01).Conclusion Modified Gegen Qinlian Decoction may play an active role in the treatment of type 2 diabetes mellitus by regulating IRE1/JNK/IRS1 signaling pathway,inhibiting insulin resistance and alleviating endoplasmic reticulum load.