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