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

doi:10.3969/j.issn.1004-616x.2015.03.007

癌变·畸变·突变 ›› 2015, Vol. 27 ›› Issue (3): 191-196.doi: 10.3969/j.issn.1004-616x.2015.03.007

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

刘颖, 傅晗, 师腾瑞, 刘江正, 王欣, 海春旭

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

收稿日期:2015-03-12 修回日期:2015-04-16 出版日期:2015-05-30 发布日期:2015-05-30
通讯作者: 海春旭,E-mail:cx-hai@fmmu.edu.cn E-mail:cx-hai@fmmu.edu.cn
作者简介:刘颖,E-mail:liuyinglyzy@163.com
基金资助:
国家自然科学基金(81473010,3140040159)

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

LIU Ying, FU Han, SHI Tengrui, LIU Jiangzheng, WANG Xin, HAI Chunxu

Department of Toxicology, School of Military Preventive Medicine, Shaanxi Provincial Key Laboratory of Free Radical Biology and Medicine, the Fourth Military Medical University, Xi'an 710032, Shaanxi, China

Received:2015-03-12 Revised:2015-04-16 Online:2015-05-30 Published:2015-05-30

摘要/Abstract

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(mtTFA)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mtTFA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/mtTFA分子通路的功能障碍可能发挥了重要作用。

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

Abstract:

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 mtTFA 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 mtTFA were decreased by 20%-30%. CONCLUSION:Oxidative stress and dysfunction of Nrf2/NRF-1/mtTFA axis may play important roles in the development of insulin resistance induced by a high fat diet.

Key words: insulin resistance, oxidative stress, Nrf2, NRF-1, mtTFA

中图分类号:

R587.1

刘颖, 傅晗, 师腾瑞, 刘江正, 王欣, 海春旭. 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[J]. 癌变·畸变·突变, 2015, 27(3): 191-196.

LIU Ying, FU Han, SHI Tengrui, LIU Jiangzheng, WANG Xin, HAI Chunxu. 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[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2015, 27(3): 191-196.

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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

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