缺血后处理对肝缺血再灌注损伤后磷脂酰肌醇-3激酶和细胞外信号调节激酶的影响和意义

摘要

目的 观察缺血后处理对肝缺血再灌注后磷脂酰肌醇-3激酶(PI3K)和细胞外信号调节激酶1/2(ERK1/2)表达的影响,探讨肝缺血后处理的作用机制 方法 采用大鼠70％肝缺血再灌注损伤模型,进行3次循环的再灌注1 min-阳断1 min的缺血后处理,观察假手术(S)组、LY294002+假手术(LY+S)组、PD98059+假手术(PD+S)组,缺血再灌注(IR)组、缺血后处理(IPO)组、LY294002+缺血后处理(LY +IPO )组和PD98059+IPO( PD+IPO)组的肝功能、细胞凋亡、Akt和ERK1/2磷酸化程度的变化.结果 缺血后处理能明显减轻缺血再灌注造成的肝功能损害,增加Akt和ERK1/2的磷酸化程度,应用LY294002或PD98059后都可以取消IPO的作用 结论 缺血后处理可能通过澈活PI3K和ERK1/2减轻肝缺血再灌注损伤.%Objective To observe the effect of ischemic postconditioning on phosphatidylinositol-3-OH kinase (PI3K) and extracellular signal-regulated protein kinase l/2(ERKl/2) in rats after hepatic ischemia reperfusion in rats and investigate the mechanism of ischemic postcoditioning of the liver.Methods Three cycles of 1 min-off-1 min-on ischemic postconditioning regime were used in a rat model of 70% hepatic ischemia-reperfusion injury.The changes in the liver function,he-patocyte apoptosis,phosphorylation of Akt and ERK1/2 were assessed in rats treated with sham operation,LY294002+sham operation (LY + S),PD98059 + sham operation (PD + S),ischemia reperfusion (IR),ischemic postconditioning (IPO),LY294002+ ischemic postconditioning (LY+IPO),or PD98059+ischemic postconditioning (PD+IPO).Results Ischemic postconditioning significantly alleviated hepatic ischemia-reperfusion-induced liver function injury and hepatocyte apoptosis and increased phophorylation of Akt and ERK1/2.LY294002 and PD98059 antagonized the effects of ischemic postconditioning in the liver.Conclusion Activation of PI3K and ERK1/2 may mediate the protective effect of ischemic postconditioning against hepatic ischemia-reperfusion injury in rats.