N-乙酰半胱氨酸对游离脂肪酸诱导的胰岛素抵抗的影响

Evaluation of free fatty acid-induced insulin resistance with euglycemic-hyperinsulinemic clamping.

目的验证游离脂肪酸(FFA)诱导胰岛素抵抗,探讨抗氧化剂N-乙酰半胱氨酸(NAC)对FFA诱导的胰岛素抵抗的影响。方法2004年8月至2005年1月在中国医科大学附属盛京医院将24只正常Wistar大鼠随机分为4组,每组6只,分别静脉输注脂肪乳(IH)、NAC、IH+NAC和生理盐水。清醒状态下行高胰岛素-正血糖钳夹,并测定血糖、FFA、胰岛素和丙二醛(MDA),计算胰岛素敏感指数(ISI)及葡萄糖输注率(GIR)。结果IH组FFA和MDA较其他3组显著增高,ISI及GIR显著降低。IH+NAC组FFA和MDA显著降低,GIR显著增高。结论FFA浓度增高可诱导胰岛素抵抗,NAC可显著降低FFA和MDA浓度,改善胰岛素抵抗。

Objective To prove insulin resistance-induced by free fatty acid （FFA）with hyperinsulinemic-euglycemic clamp and assess the prevention from this resistance by N-acetylcysteine （NAC）. Methods Twenty-four female Wistar rats were randomly divided into 4 groups, each of which received infusion of IH （ 20% intralipid ＋ 20 U/mL heparin ）, IH ＋ NAC,NAC, and saline respectively for 7 h. Two-hour hyperinsulinemic-euglycemic clamp was made after 5h infusion. During the infusion and clamp the rats were awake. Blood samples were taken for measuring insulin, FFA and maleic dialdehyde（MDA） at 0 min ,280 min,290 min, 300 min, 340 min,380 min,400 min,410 min and 420 min. The insulin sensitive index was calculated. Results Plasma FFA and MDA levels in IH group were significantly elevated compared with those in control, IH ＋ NAC and NAC groups, P 〈 0. 05. It showed that NAC infusion decreased the levels of FFA and MDA induced by IH,P 〈 0. 05. The ISI in the IH group was significantly lower than the control,P 〈 0. 05. In clamp state, the glucose infusion rate （GIR）in the IH group was significantly lower than the control, P 〈0. 05. The GIR of IH ＋ NAC group was significantly higher than that of the IH group ,P 〈0.05 ,while similar to the level of the control group. Conclusion The elevation of FFA caused by intralipid infusion induces insulin resistance;the antioxidant NAC significantly decreases the levels of FFA and MDA induced by IH and prevents insulin resistance.