水杨酸钠改善大鼠胰岛素抵抗的实验研究

Experimental study on sodium salicylate improved insulin resistance in rats

目的探讨水杨酸钠对大鼠胰岛素抵抗的影响及作用机制。方法分别给大鼠静脉输注脂肪乳+肝素、脂肪乳+肝素+水杨酸钠和生理盐水7h,并在输注的最后2h,行清醒状态高胰岛素-正血糖钳夹试验,测定血浆葡萄糖、游离脂肪酸(FFA)、胰岛素、C-肽和丙二醛(MDA)水平,检测肝脏、肌肉和胰腺中MDA含量及谷胱甘肽过氧化物酶(GSH-PX)活性。结果脂肪乳输注组葡萄糖输注率(GIR)是生理盐水输注组的45%,输注水杨酸钠可使GIR提高1.3倍(P<0.01)。与生理盐水输注组比较,脂肪乳输注组血浆、肝脏、肌肉和胰腺中MDA水平增加了2～4倍(P<0.01);肝脏、肌肉和胰腺GSH-PX活性降低45%～50%(P<0.01)。水杨酸钠输注使MDA水平较脂肪乳输注组降低了62%～66%(P<0.01),GSH-PX活性升高35%～38%(P<0.05)。结论FFA增高引起机体氧化应激增强,可能是导致胰岛素抵抗发生的机制之一,应用水杨酸钠,大鼠氧化应激减弱,胰岛素抵抗改善,抗炎药物水杨酸钠可能通过降低氧化应激途径而发挥改善胰岛素抵抗及保护胰岛β细胞功能的作用。

[Objective] To investigate the mechanism and effects of intravenously infused sodium salicy!ate on insulin resistance in rats, [Methods] Intralipid ＋ Heparin （IH）, Sodium Salicylate＋ Intralipid ＋ Heparin （SI）, and saline （SAL） were intravenously infused for 7 hours in rats. During the last 2 hours of the infusion, insulin sensitivity was measured with glucose infusion rate （GIR）, plasma glucose, free fatty acids （FFA）, insulin, C-peptide and MDA were detected, the levels of MDA and the activity of GSH-PX in liver, muscle and pancreas were examined. [Resuits] During hyperinsulinemic-euglycemic clamp, infusion of intralipid resulted in a 55% reduction in GIR, while Compared with IH group, GIR increased 1.3 times in rats with infusion of sodium salicylate. Compared with SAL, there were elevated 2-4 times of MDA in plasma, liver, muscle and pancreas in rats with IH （P 〈0.01）, and the activity of GSH-PX in liver, muscle and pancreas decreased 45%-50% （P 〈0.01）. Compared with IH, the levels of MDA in plasma, liver, muscle and pancreas decreased 62%-66% （P 〈0.01）, the activity of GSH-PX increased 35%-38% （P 〈0.05） in rats with SI. [Conclusion] Oxidative stress may be one of the mechanisms of insulin resistance induced by elevation of FFA, and there were decrease of oxidative stress and insulin resistance in rats with sodium salicylate. Perhaps sodium salicylate improved insulin resistance and protected β cell through decreasing oxidative stress.