IRS1/PI3K/Akt信号通路在Ang(1～7)调节非酒精性脂肪性肝炎中的作用  

Role of IRS1/PI3k/Akt signaling pathway in Ang(1～7) regulating nonalcoholic steatohepatitis

作　　者：张艺军 邹瑞[2] 钟武装 蔡敏捷 许桂英 乐德 刘岗 ZHANG Yi-Jun;ZOU Rui;ZHONG Wu-Zhuang(Department of Gernerology, the General Hospital of Southern Theatre Command of PLA, Guangzhou 510010, Guangdong, China)

机构地区：[1]中国人民解放军南部战区总医院干部病房二科,广东广州510010 [2]广州医科大学附属口腔医院,广州口腔疾病研究所,口腔医学重点实验室

出　　处：《中国老年学杂志》2019年第20期5081-5085,共5页Chinese Journal of Gerontology

基　　金：广州市科技计划项目科学研究专项(201510010176);军委保健专项基金面上项目(17BJZ19)

摘　　要：目的 探讨胰岛素受体底物(IRS)1/磷脂酰肌醇3激酶(PI3K)/丝/苏氨酸激酶(Akt)信号通路在血管紧张素(Ang)(1~7)体外调节非酒精性脂肪性肝炎中的作用机制。方法 诱导L02肝细胞脂肪变;Ang(1~7)及Ang(1~7)+MAS拮抗剂(A779)干预脂肪变L02肝细胞,并设立AngⅡ干预;培养24h后采用酶联免疫吸附试验(ELISA)分别检测细胞培养上清液中肿瘤坏死因子(TNF)-α、葡萄糖转运蛋白(GLUT)4、胆固醇、谷丙转氨酶(ALT)含量;逆转录-聚合酶链反应(RT-PCR)和Western印迹检测IRS1基因及活性及PI3K、Akt磷酸化表达水平。结果 Ang(1~7)组中总胆固醇、ALT含量降低,GLUT4含量升高,与阴性对照组相比差异有统计学意义(P<0.05);且IRS1基因及活性增强,磷酸化PI3K、Akt表达水平升高,TNF-α表达量下降。AngⅡ组总胆固醇、ALT含量升高,GLUT4含量降低,与阴性对照组相比差异有统计学意义(P<0.05);且IRS1基因及活性降低,磷酸化PI3K、Akt表达水平降低,TNF-α表达量升高。Ang(1~7)组的保护作用能被A779抑制。结论 Ang(1~7)可以通过IRS1/PI3K/Akt信号通路抑制TNF-α活性,增加GLUT4含量,发挥改善非酒精性脂肪性肝炎胰岛素抵抗的作用。Objective To investigate the mechanism of IRS1/PI3K/Akt signaling pathway in the process of Ang(1~7) regulating non-alcoholic steatohepatitis in vitro. Methods Adipogenic differentiatied hepatocytes L02 were intervened with three groups of agents, Ang(1~7), Ang(1~7)+MAS antagonists (A779) and AngⅡ, respectively. The levels of TNF-α, GLUT4 (glucose transporter), total cholesterol and alkaline aminotransferase (ALT) in cell culture supernatants were detected by ELISA after 24 h. The gene expression and protein activity of IRS1, the phosphorylated levels of PI3K and Akt were analyzed with RT-PCR and Western blot. Results In Ang (1~7) group, the level of total cholesterol and ALT increased and GLUT4 level decreased, which were significantly different from the negative control group ( P <0.05). The IRS1 gene expression level and protein activity were elevated, and the levels of phosphorylated PI3K and phosphorylated Akt were increased. TNF-α expression level was decreased. In the AngⅡ group, the levels of total cholesterol and ALT were increased, and the GLUT4 level was decreased, which were significantly different from the negative control group ( P <0.05). Meanwhile, the IRS1 gene expression level and protein activity were decreased, and the levels of phosphorylated PI3K and phosphorylated Akt were decreased. TNF-α expression level was increased. The protective effect of Ang (1~7) could be inhibited by A779. Conclusions Ang (1~7) could stimulate IRS1/PI3K/Akt signaling pathway to inhibit the activity of TNF-α, and increase the level of glucose transporter. The effects could decrease insulin resistance and improve nonalcoholic steatohepatitis.

关 键 词：胰岛素受体底物(IRS)1/磷脂酰肌醇3激酶(PI3K)/丝/苏氨酸激酶(Akt) 血管紧张素Ang(1~7) 非酒精性脂肪性肝炎 

分 类 号：R575[医药卫生—消化系统]