基础医学与临床 ›› 2008, Vol. 28 ›› Issue (6): 549-552.

• 研究论文 • 上一篇    下一篇

N-乙酰半胱氨酸改善高游离脂肪酸所致大鼠外周胰岛素抵抗

王冰 李宏亮 杨文英 萧建中 杜瑞琴 白秀平 潘琳   

  1. 北京中日友好医院内分泌科 中日友好医院内分泌科 中日友好医院内分泌科 中日友好医院内分泌科 中日友好医院内分泌科 中日友好医院内分泌科 中日友好医院临床研究所细胞生物实验室
  • 收稿日期:2007-07-11 修回日期:2007-12-13 出版日期:2008-06-25 发布日期:2008-06-25
  • 通讯作者: 王冰

NAC on the improvement of insulin resistance induced by FFA in rats

Bing WANG, Hong-liang LI, Wen-ying YANG, Jian-zhong XIAO, Rui-qin DU, Xiu-ping BAI, Lin PAN   

  1. Dept. of Endocrinology,Chian japan Friendship Hospital
  • Received:2007-07-11 Revised:2007-12-13 Online:2008-06-25 Published:2008-06-25
  • Contact: Bing WANG,

摘要: 目的 探讨N-乙酰半胱氨酸(NAC)对高游离脂肪酸(FFA)导致的外周胰岛素抵抗的影响及机制。方法SD大鼠随机分为对照组(NS组,12只)、脂肪乳输注组(FFA组,13只)和脂肪乳+NAC组(NAC组,12只)。输注48h,(1)测血浆硝基酪氨酸,丙二醛(MDA)和还原型谷胱甘肽(GSH)水平;(2)高胰岛素正糖钳夹试验,评价外周胰岛素抵抗程度;(3)实时荧光定量PCR方法测定肌肉组织胰岛素受体底物-1(IRS-1)、胰岛素受体底物-2(IRS-2)mRNA表达。结果 (1)FFA组硝基酪氨酸,MDA高于NS组,GSH低于NS组,NAC分别改善28.6%,33.1%,22.9%(P均<0.05);(2)FFA组葡萄糖输注率(GIR)比NS组降低(P<0.05),用NAC后GIR升高36.6%(P<0.05);(3) FFA组肌肉组织IRS-1、IRS-2mRNA表达比NS组降低87.7%、50.7%(P均<0.05);NAC组肌肉组织IRS-1、IRS-2表达比FFA组增加370.1% 、46.2%,(P均<0.05)。结论NAC干预能改善高FFA所致的外周胰岛素信号传导障碍,逆转外周胰岛素抵抗,可能与NAC纠正机体氧化及抗氧化失衡有关。

关键词: N-乙酰半胱氨酸, 胰岛素抵抗, 实时荧光定量PCR

Abstract: Objective:To investigate the changes of peripheral insulin resistance after lipid infusion and the effect of N-acetylcystein(NAC) intervention. Methods:Thirty-seven normal male SD rats, eight weeks old, were randomly divided into three groups, FFA group ,NS group and NAC group(using NAC 300mg·kg-1·d-1 two weeks before infusion). Catheters were implanted under pentobarbital anesthesia in the right atrium via the jugular vein and the left carotid artery. A technique for a 48-h infusion in unrestrained rats was used for triglyceride and heparin or saline infusion. The infusion period started on day 2 after surgery. After 48-h infusion, we determined free fat acid(FFA),nitrotyrosine,malonaldehyde(MDA),reduced glutathione hormone (GSH) level in plasma. The glucose infusion rat(GIR) was measured by hyperinsulinemia euglycemic clamp to evaluated the perpherial insulin resistance. The expressions of IRS-1,IRS-2 gene in muscle were detected by real time PCR. Results:(1)The FFA,nitrotyrosine and MDA concentrations in FFA group were higher than in NS group,but GSH level in plasma was lower.NAC intervention could reverse these effects.(2)The GIR was decreased significantly in FFA group compared with NS group (8.34±1.8mg.min-1.kg-1 vs 13.56±1.7 mg.min-1.kg-1,P<0.05), NAC intervention can reverse these effect(11.39±1.6mg.min-1.kg-1 vs8.34±1.8mg.min-1.kg-1,P<0.05).(3)The gene expression of IRS-1 was significantly decreased by 87.7% in FFA group, and the expressions of IRS-2 was decreased by 50.7% (all P<0.05).In contrast, the expressions of IRS-1,IRS-2 in NAC group reversed 370.1% and 46.2% respectively than in FFA group(all P<0.05). Conclusions:NAC intervension as a possible could increase the gene expression of insulin signal transduction molecules in muscle which might relate with the antioxidant effects of NAC.

Key words: N-acetylcystein, insulin resistance, real-time PCR