水杨酸钠对胰岛素抵抗大鼠氧化应激水平的影响

目的探讨水杨酸钠对胰岛素抵抗大鼠胰岛素敏感性的影响及作用机制。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，部分大鼠在输液的最后2h同时行清醒状态高胰岛素一正血糖钳夹试验，测定血浆葡萄糖、游离脂肪酸（FFA）、胰岛素、C肽、丙二醛（MDA）水平，检测肝脏、肌肉中MI）A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、肌肉中MDA水平增加了2～4倍（P〈0．01）；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。应用水杨酸钠后大鼠氧化应激减弱，胰岛素抵抗改善，故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的作用。

Effects of sodium salicylate on the levels of oxidative stress in insulin resistant rats

AIM To investigate the mechanism and effects of intravenously infused sodium salicylate on insulin resistance in rats, respectively. METHODS Intralipid ＋ heparin （IH）, sodium salicylate ＋ intralipid ＋ heparin （SI）, and normal saline （SAL） were intravenously infused for 7 h in rats. During the last 2 h of the infusion, insulin sensitivity was measured with glucose infusion rate （GIR） by using hyperinsulinemic-euglucemic clamp. Plasma glucose, free fatty acid （FFA）, insulin , C-peptide and malondialdehyde （MDA）were detected. The levels of MDA and the activity of glutathione peroxidase （GSH-PX） in liver and muscle were examined. RESULTS During hyperinsulinemic-euglycemic clamp, infusion of intralipid resulted in a 55 % reduction in GIR. Compared with IH group, GIR increased 1.3 times in rats with infusion of sodium salieylate. Compared with SAL group, there were elevation by 2 - 4 times of MDA in plasma, liver and muscle in rats in IH group（ P 〈 0.01）, and the activity of GSH-PX in liver and muscle decreased by 45% - 50% （ P 〈 0.01）. Compared with IH group, the levels of MDA in plasma, liver, muscle decreased by 62% - 66 % （ P 〈 0.01 ） and the activity of GSH-PX increased by 35 % - 38 % （ P 〈 0.05） in rats in SI group. CONCLUSION Oxidative stress may be one of the mechanisms of insulin resistance induced by elevation of FFA. The oxidative stress and insulin resistance can be decreased by sodium salicylate. The improvement of insulin resistance by sodium salicylate may be induced by its＇ effect on inhibiting the oxidative stress pathway.