姜黄素激活Nrf2抗氧化系统缓解百草枯诱导的胰岛素抵抗  

Curcumin-induced Activation of the Nrf2 Antioxidant System Attenuates Paraquat-induced Insulin Resistance

作　　者：杨含艳 展平[1] 任丽伟[1] 于志文[1] 

机构地区：[1]福建中医药大学药学院,福建福州350122

出　　处：《海峡药学》2015年第3期24-27,共4页Strait Pharmaceutical Journal

基　　金：国家自然科学基金(No 81270886)

摘　　要：目的观察姜黄素是否具有改善百草枯(paraquat,PQ)所致氧化应激诱导的胰岛素抵抗作用并探讨其改善胰岛素抵抗的效应机理。方法将实验小鼠随机分成对照组(Control组),百草枯组(PQ组)以及PQ加姜黄素组(Cur组)。PQ和Cur组连续腹腔注射百草枯7天造模成功后。Cur组继续Cur灌胃干预。7天后,取胰岛素敏感组织肌肉,用蛋白免疫印迹方法(Western blot,WB)检测蛋白水平和磷酸化变化,并检测脂质过氧化指标MDA。结果在PQ诱导的小鼠胰岛素抵抗模型中,姜黄素可改善小鼠葡萄糖耐量并对抗PQ所致的胰岛素信号蛋白PKBSer473磷酸化损害;姜黄素还可明显降低肌肉MDA水平,激活小鼠Nrf2系统,促进Nrf2核转位和NQO-1的表达,同时能增强IкBα的水平,缓解氧化应激及炎症反应。结论姜黄素通过增强内源性Nrf2系统功能和胰岛素信号水平,对抗PQ诱导的氧化应激,是其缓解胰岛素抵抗的重要机理。OBJECTIVE To examine the effect of curcumin on the paraquat-mediated oxidative stress and insulin resistance,and to further explore the working mechanism underlying its effect.METHODS Thirty mice were randomly divided into 3 groups： control group,paraquat group and curcumin intervention group.Paraquat group and curcumin intervention group were continuously intraperitoneal injection of paraquat for 7 days to induce the models of insulin resistance.The curcumin intervention group was continuously gavaged with curcumin for another 7days.Then,all mice were euthanized for muscle collection.The protein and phosphorylation levels in muscle tissue were examed by Western blot and the content of malonaldchyde（MDA） indicated for lipid peroxidation was determined.Results Curcumin improved the glucose tolerance in paraquat-induced insulin resistance in mice together with attenuation of PQ-caused impairment in PKBSer473 phosphorylation.Curcumin also significantly reduced muscular MDA level,promoting the Nrf2 translocation into nucleus,along with the enhanced expression of quinine oxidoreductase1（NQO-1）.Curcumin also increased IкBαcontent.Conclusion Curcumin enhances the function of endogenous Nrf2 system and insulin signaling to against PQ-induced oxidative stress and inflammation which may be the mechanisms of curcumin to attenuate insulin resistance.

关 键 词：姜黄素 PQ NRF2 抗氧化作用 胰岛素抵抗 

分 类 号：R969.4[医药卫生—药理学]