基于INSR/PI3K/AKT信号通路的加味温胆汤抗雌性幼鼠营养性肥胖机制研究  

Mechanism of Modified Wendan Decoction Against Nutritional Obesity in Young Female Rats:An Exploration Based on INSR/PI3K/Akt Signaling Pathway

作　　者：姚凤云[1] 钟琦 吴莹莹[1] 左铮云 黄艳美 刘春花[1] 王炳志 Yao Fengyun;Zhong Qi;Wu Yingying;Zuo Zhengyun;Huang Yanmei;Liu Chunhua;Wang Bingzhi(College of Pharmacy,Jiangxi University of Chinese Medicine,Nanchang 330004;Formula-Pattern Research Center,Nanchang 330004)

机构地区：[1]江西中医药大学中医学院,南昌330004 [2]方证研究中心,南昌330004

出　　处：《中药药理与临床》2021年第3期26-29,共4页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金项目(编号:81660766);江西省自然科学基金项目(编号:20202BAB206068);江西省“双一流”学科(中医学)建设资助项目(编号:JXSYLXK-ZHYI051);江西省中医药中青年骨干人才培养计划项目(编号:赣中医药科教字[2020]2号)。

摘　　要：目的:通过观察加味温胆汤对营养性肥胖幼鼠INSR/PI3K/AKT信号通路相关指标含量及mRNA表达的影响,探讨该方抗雌性幼鼠营养性肥胖的机制。方法:60只SD雌性幼鼠按体质量随机分为正常对照组、模型对照组、加味温胆汤2.2、4.3、8.6 g/kg组;采用"高脂乳剂+拌油饲料"喂养复制幼鼠营养性肥胖模型,灌胃给药,连续5 w,分离骨骼肌组织,采用酶联免疫法(ELISA)分别检测骨骼肌INS、胰岛素受体(INSR)、葡萄糖转运体4(GLUT4)含量,采用实时荧光定量PCR法(Real-time PCR)检测骨骼肌胰岛素受体底物2(Irs2)、磷脂酰肌醇3激酶(Pi3k)、蛋白激酶B(Akt)、糖原合成酶激酶3β(Gsk3β)和Glut4 mRNA表达水平。结果:与正常对照组比较,模型对照组幼鼠体质量、脂肪指数、Lee’s指数、骨骼肌INS含量显著升高;骨骼肌Gsk3βmRNA表达显著上调,而骨骼肌Pi3k、Akt和Glut4 mRNA表达显著下调(P<0.01)。与模型对照组比较,加味温胆汤8.6 g/kg组骨骼肌INS含量与Gsk3βmRNA表达水平降低、Pi3k mRNA表达升高;加味温胆汤4.3 g/kg组脂肪指数、Lee’s指数、骨骼肌INS含量、Irs2与Gsk3βmRNA表达降低,而骨骼肌Pi3k、Akt、Glut4 mRNA表达上调;加味温胆汤2.2 g/kg组骨骼肌INS含量下降(P<0.05或P<0.01)。结论:加味温胆汤抗雌性幼鼠营养性肥胖的机制可能与改善骨骼肌胰岛素抵抗(IR)、下调胰岛素受体、PI3K/AKT信号通路Gsk3βmRNA表达和上调Pi3k、Akt、Glut4mRNA表达有关,其中加味温胆汤4.3 g/kg组作用最佳。Objective:To observe the effects of modified Wendan Decoction on indicators related to the insulin receptor(INSR)/phosphotidylinositol 3 kinase(PI3 K)/protein kinase B(Akt)signaling pathway and their mRNA expression in young female rats with nutritional obesity and explore the mechanism of modified Wendan Decoction in inhibiting nutritional obesity.Methods:Sixty young female SD rats were randomly divided into five groups according to their body weight,namely normal control group,model group,and low-(2.2 g/kg),medium-(4.3 g/kg),and high-dose(8.6 g/kg)modified Wendan Decoction groups.The nutritional obesity model was established via intragastric administration of high fat emulsion and feed mixed with oil for five weeks.The skeletal muscle was separated and the contents of insulin(INS),INSR,glucose transporter 4(GLUT4)were measured by enzyme-linked immunosorbent assay(ELISA),followed by the detection of mRNA expression levels of insulin receptor substrate 2(IRS2),PI3 K,Akt2,glycogen synthase kinase 3β(GSK3β)and GLUT4 in the skeletal muscle by real-time polymerase chain reaction(Real-time PCR).Results:Compared with the normal control group,the model group displayed obviously increased body mass,fat and Lee’s indexes,INS content in skeletal muscle,up-regulated GSK3βmRNA expression,down-regulated PI3 K,Akt,and GLUT4 mRNA expression(P<0.01).The comparison with the model group revealed that the INS content and the GSK3βmRNA expression were reduced in the high-dose modified Wendan Decoction group,whereas the expression level of PI3 K was increased.The fat index,Lee’s index,the INS content,and the IRS2 and GSK3βmRNA expression in the medium-dose modified Wendan Decoction group declined,while the mRNA expression levels of PI3 K,Akt and GLUT4 rose.In the low-dose modified Wendan Decoction group,the INS content was decreased(P<0.05 or P<0.01).Conclusion:The mechanism of modified Wendan Decoction against nutritional obesity in young female rats is possibly related to the improvement of insulin resistance(IR),down-regu

关 键 词：加味温胆汤 营养性肥胖 胰岛素抵抗 磷脂酰肌醇3激酶/蛋白激酶B 

分 类 号：R285.5[医药卫生—中药学]