游离脂肪酸对肝脏氧化应激及胰岛素抵抗的影响  

Effects of free fatty acid elevation on hepatic insulin resistance and hepatic oxidative stress

作　　者：卢雁[1] 韩萍[1] 赵晟[1] 张咏言[1] 何冰[1] 张微[1] 

机构地区：[1]中国医科大学附属盛京医院内分泌科,辽宁省沈阳市110004

出　　处：《世界华人消化杂志》2009年第23期2405-2408,共4页World Chinese Journal of Digestology

基　　金：辽宁省教育委员会基金资助项目;No20060999~~

摘　　要：目的:研究游离脂肪酸(FFA)慢性升高对肝脏胰岛素抵抗的影响,探讨氧化应激在其中的作用.方法:给Wistar大鼠分别静脉输注脂肪乳加肝素(IH组)和单纯输注生理盐水(SAL组)48h,在输注的最后2h,清醒状态下行高胰岛素-正血糖钳夹试验,观察延时输注脂肪乳导致的高FFA对葡萄糖利用率(葡萄糖输注率,GIR)的影响,并取肝组织测定羰基蛋白、肝细胞膜和细胞质PKC-δ的含量.结果:在高胰岛素-正血糖钳夹状态,IH输注组与SAL组比较,血清FFA增加4.3倍(P<0.001),羰基蛋白增加3.2倍,GIR下降58.6%(均P<0.001);48h的IH输注使肝细胞膜的PKC-δ/胞质PKC-δ比值增加4.0倍(P<0.001).结论:FFA慢性升高导致了肝脏GIR下降,葡萄糖的利用障碍,肝脏的PKC-δ向细胞膜转位增加,说明在慢性高FFA导致的肝脏胰岛素抵抗中,氧化应激反应起了重要的作用.AIM：To investigate the effects of long-term elevation of free fatty acids（FFA）on hepatic insulin resistance and hepatic oxidative stress. METHODS：A total of 32 Wistar rats were divided into two groups and given an intravenous infusion of intralipid plus heparin（IH）and saline （SAL）,respectively.Two hours before the end of the infusion,a hyperinsulinemic-euglycemic clamp was performed to examine the ability of FFA to induce hepatic insulin resistance.After the clamp,liver tissue samples were taken to determine the protein carbonyl content by DNPH （2,4-dinitrophenylhydrazine）colorimetry and the content of protein kinase C-δby Western blot. RESULTS：Compared to SAL infusion,IH infu-sion resulted in an increase in plasma FFA level by 4.3 folds（P〈0.001）,hepatic protein carbonyl content by 3.2 folds,and the membrane/cytosol ratio of PKC-δby 4.0 folds（P〈0.001）. CONCLUSION：Long-term elevation of FFA induces elevation of hepatic protein carbonyl content,PKC-δtranslocation and insulin resistance, suggesting that PKC-δplays an important role in FFA-induced hepatic insulin resistance.

关 键 词：游离脂肪酸 胰岛素抵抗 葡萄糖输注率 羰基蛋白 蛋白激酶C-δ 

分 类 号：R587.1[医药卫生—内分泌]