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

NAC decreases insulin resistance induced by FFA in rats

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48 h,(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<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-2 mRNA表达比NS组降低87.7%、50.7%(P<0.05);NAC组肌肉组织IRS-1、IRS-2表达比FFA组增加370.1%、46.2%,(P<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。

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 into NAC 300 mg/（kg, d） two weeks before infusion）. Catheters were implanted into right atrium via the jugular vein and 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. 48-h after 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 that in NS group,but GSH level in plasma was lower. NAC intervention could reverse these effects. （2）GIR was decreased significantly in FFA group as compared with NS group [ （8. 34 ± 1.8） mg/（ min ·ks） ] vs [ （ 13.56 ± 1.7 ） mg/（ min · ks） ], （ P 〈 0. 05 ）, NAC intervention can reverse these effect [ （ 11. 39 ± 1. 6） mg/（ min · ks） ] vs [ （8. 34 ± 1.8 ） mg/（ min· ks） ], （ P 〈 0. 05 ）. （ 3 ） The gene expression of IRS-1 was 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 ）. Conclusion NAC intervension may increase the gene expression of insulin sig- nal transduction molecules in muscle which may explain the antioxidant effects of NAC.