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

Effect of ischemic postconditioning on phosphatidylinositol-3-OH kinase and extracellular signal-regulated protein kinase in rats with hepatic ischemia-reperfusion injury

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-阻断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激活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 1/2（ERK1/2） 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,hepatocyte 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.