Apocynin改善TNF-α诱导肝细胞胰岛素抵抗的机制研究

中国临床药理学与治疗学 ›› 2010, Vol. 15 ›› Issue (10): 1116-1121.

Apocynin改善TNF-α诱导肝细胞胰岛素抵抗的机制研究

李兰芳, 郭玉, 唐国涛, 喻翠云, 陈临溪

南华大学药物药理研究所,衡阳 421001,湖南

收稿日期:2010-08-02 修回日期:2010-10-23 发布日期:2020-09-16
通讯作者: 陈临溪,男,教授,研究方向:心血管药理与药物蛋白质组学。Tel: 0734-8281408 E-mail: chenlinxi@tom.com
作者简介:李兰芳,女,博士,研究方向:氧化应激与胰岛素抵抗。Tel: 13264130629 E-mail: wjliu829@yahoo.cn
基金资助:
国家自然科学基金项目(30901577);湖南省衡阳市科技局项目(2009KJ14)

Mechanism of Apocynin improves insulin resistance induced by TNF-α in HepG2 cells

LI Lan-fang, YUO Yu, TANG Guo-tao, YU Cui-yun, CHEN Lin-xi

Institute of Pharmacy and Pharmacology, Nanhua University, Hengyang 421001, Hunan, China

Received:2010-08-02 Revised:2010-10-23 Published:2020-09-16

摘要/Abstract

摘要： 目的: 探讨NADPH氧化酶(NOX)的P47^PHOX亚基膜转位的抑制剂Apocynin对TNF-α诱导的胰岛素抵抗以及氧化应激水平的影响。方法: 实验分为4组:对照组、TNF-α(4 ng/mL)处理组、TNF-α+Apocynin(100 μmol/L)处理组和Apocynin(100 μmol/L)处理组。蒽酮法检测细胞内糖原合成;用DCFH-DA探针标记,流式细胞术检测细胞内活性氧的水平;Western blotting检测JNK、p-JNK、IRS1、p-IRS1的表达。结果: 与对照组比较,TNF-α刺激HepG2后活性氧水平显著增加,细胞内糖原合成障碍。Apocynin能显著降低TNF-α诱导的细胞内活性氧的水平,并促进细胞内糖原合成。TNF-α激活JNK,同时抑制胰岛素信号通路,Apocynin能抑制TNF-α对JNK的激活,并且促进胰岛素信号通路敏感性。单独用Apocynin处理对细胞内活性氧和糖原合成以及下游信号通路均无显著影响。结论: Apocynin能降低TNF-α诱导的细胞内活性氧的水平,改善TNF-α诱导肝细胞胰岛素抵抗状态。

关键词: 胰岛素抵抗, 氧化应激, TNF-α

Abstract: AIM: To investigate the effects of Apocynin on oxidative stress and insulin resistance induced by TNF-α. METHODS: Cells were divided into control group,TNF-α(4 ng/mL)treatment group,TNF-α+Apocynin(100 μmol/L)treatment group,Apocynin(100 μmol/L)group. The insulin resistance cell model was induced by TNF-α(4 ng/mL)to stimulate human hepatoma carcinoma cell HepG2. The intracellular glycogen was detected using a glucose oxidase assay kit. The level of intracellular reactive oxygen species (ROS) was detected by DCFH-DA fluorescent probe and flow cytometry. The expressions of JNK, p-JNK, IRS1 and p-IRS1 were observed by Western blotting. RESULTS: Compared with the control group, the level of ROS in HepG2 Cells in TNF-α treatment group was significantly increased and the level of intracellular glycogen in cell was decreased, TNF-α activated JNK and inhibited insulin signal pathway,and Apocynin could reverse those effects induced by TNF-α.Apocynin(100 μmol/L)group had no significant effects on ROS,glycogen synthesis and signal pathway. CONCLUSION: Apocynin can decrease the level of ROS in cell and improve insulin resistance condition induced by TNF-α in HepG2 cell.

Key words: Insulin resistance, Oxidative stress, TNF-α

中图分类号:

R965.2

李兰芳, 郭玉, 唐国涛, 喻翠云, 陈临溪. Apocynin改善TNF-α诱导肝细胞胰岛素抵抗的机制研究[J]. 中国临床药理学与治疗学, 2010, 15(10): 1116-1121.

LI Lan-fang, YUO Yu, TANG Guo-tao, YU Cui-yun, CHEN Lin-xi. Mechanism of Apocynin improves insulin resistance induced by TNF-α in HepG2 cells[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(10): 1116-1121.

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