高脂饲料喂饲C57小鼠诱发胰岛素抵抗过程中肝脏氧化应激水平及Nrf2、NRF-1和mtTFA蛋白表达的变化  

Effect of high fat diet on oxidative stress and protein expressions of Nrf2, NRF-1 and mtTFA in liver of C57 mice during hepatic insulin resistance

作　　者：刘颖[1] 傅晗[1] 师腾瑞 刘江正[1] 王欣[1] 海春旭[1] 

机构地区：[1]第四军医大学军事预防医学院军事毒理学教研室,陕西省自由基生物学与医学重点实验室,陕西西安710032

出　　处：《癌变．畸变．突变》2015年第3期191-196,共6页Carcinogenesis,Teratogenesis & Mutagenesis

基　　金：国家自然科学基金(81473010;3140040159)

摘　　要：目的：胰岛素抵抗是2型糖尿病的重要特征及防治难点,其机制尚未明确。本文主要研究在高脂饮食诱发的胰岛素抵抗过程中,氧化应激水平及核-线粒体轴的分子改变及可能机制。方法：以雄性C57小鼠为实验对象,随机分为2组,对照组采用正常饮食饲喂,高脂组采用含10%猪油高脂饮食饲喂以诱导胰岛素抵抗模型。检测肝脏组织活性氧、脂质过氧化物丙二醛（MDA）及脂质累积水平,测定肝组织中P-Akt、Nrf2、核呼吸因子1（NRF-1）和线粒体转录因子A（mt TFA）的蛋白表达量。结果：与对照组相比,长期使用高脂饲料喂饲动物可导致动物糖耐量及胰岛素耐量下降,使肝组织内脂质累积水平和活性氧水平显著增加,丙二醛含量增加约30%,胰岛素信号分子P-Akt蛋白表达下降约45%,Nrf2、NRF-1和mt TFA蛋白表达下降20%~30%。结论：在高脂饮食诱发胰岛素抵抗过程中,氧化应激与Nrf2/NRF-1/mt TFA分子通路的功能障碍可能发挥了重要作用。OBJECTIVE： Insulin resistance（IR） is a major characteristic of type 2 diabetes millitus which is difficult to be prevented and treated,and its pathogenesis is still uncertain. The aim of this study was to investigate the change of oxidative stress and nuclear-mitochondria axis in hepatic tissue during the process of insulin resistance induced by high-fat-diet in mice. METHODS：Male C57 mice were randomly divided into 2 groups,the mice in control group were fed with normal chow while those in high fat diet group were fed with 10% lard oil containing diet to induce insulin resistance. The hepatic reactive oxygen species level,malondialdehyde（MDA） content and lipid accumulation were tested. P-Akt,Nrf2,NRF-1 and mt TFA expression in liver tissue were determined by Western blot. RESULTS：Compared with controls,mice fed with a high fat diet could induce insulin resistance. During this process,hepatic fat and ROS accumulation were both increased,the MDA content was also elevated by about 30%. The expression of insulin signal transduction protein P-Akt was attenuated by 45% whilst the expressions of Nrf2,NRF-1 and mt TFA were decreased by 20%-30%. CONCLUSION：Oxidative stress and dysfunction of Nrf2/NRF-1/mt TFA axis may play important roles in the development of insulin resistance induced by a high fat diet.

关 键 词：胰岛素抵抗 氧化应激 NRF2 核呼吸因子1 线粒体转录因子A 

分 类 号：R587.1[医药卫生—内分泌]