水杨酸钠对胰岛素抵抗大鼠肝脏核因子-κB及炎症因子表达的影响

Effects of sodium salicylate on the expressions of NF-ΚB and inflammatory cytokine in hepatic tissue in insulin resistant rats

目的观察水杨酸钠对胰岛素抵抗大鼠肝脏胰岛素敏感性的影响。方法大鼠随机分为3组:分别给大鼠静脉输注脂肪乳(脂肪乳组),脂肪乳+水杨酸钠(实验组)和生理盐水组,并在输注后2 h,进行清醒状态下扩展高胰岛素-正血糖钳夹术,检测肝脏组织中NF-κB及IL-6、TNF-α、SOCS-3 mRNA的表达。结果脂肪乳组大鼠钳夹稳态下,内生葡萄糖产物(EGP)较基础状态降低比率仅是生理盐水组大鼠的38%,水杨酸钠提高EGP降低幅度明显(P<0.01),改善了肝脏胰岛素敏感性。脂肪乳组肝细胞核NF-κB表达量是生理盐水组2.4倍,肝组织中IL-6、TNF-α及SOCS-3 mRNA表达较生理盐水组升高,输注水杨酸钠使核内NF-κB较输注脂肪乳下降40%,炎症因子表达相应降低(P<0.01)。结论水杨酸钠可抑制肝脏组织NF-κB活化,进而降低炎症因子蓄积,发挥改善肝脏胰岛素抵抗的作用。

Objective To investigate the effects of intravenously infused sodium salicylate on hepatic insulin sensitivity in insulin resistant rats.Methods Overnight-fasted Wistar rats were subject to 7 h iv infusion of either saline or intralipid（IH） with or without salicylate.Hyperinsulinemic–euglycemic clamp with tracer infusion was performed to assess insulin-induced suppression of endogenous glucose production（EGP）.The expression of NF-κB,IL-6,TNF-α and SOCS-3mRNA in liver were examined.Results Infusion of IH markedly decreased insulin-induced suppression of EGP,which were completely prevented by salicylate co-infusion.Compared with saline group,there were elevated 2-4 times of the levels of IL-6,TNF-α,SOCS-3mRNA in liver in rats with IH,the levels of IL-6,TNF-α,SOCS-3mRNA decreased 35%-55% in sodium salicylate with intralipid group.Conclusion The efficacy of sodium salicylate had a new treatment for FFAs-induced insulin resistances.The effect of increasing insulin sensitivity by salicylate in part may be secondary to suppress the activation of NF-κB and downstream cytokine production in liver.