ERK1/2激活参与乳化异氟醚后处理的脑保护作用

目的观察细胞外信号调节激酶1/2(ERK1/2)的激活在8%乳化异氟醚后处理对大鼠局灶性脑缺血-再灌注损伤中的作用。方法健康成年雄性SD大鼠48只,随机均分为六组:假手术组(S组)、缺血-再灌注组(IR组)、乳化异氟醚后处理组(EI组)、ERK抑制剂PD98059组(PD组)、乳化异氟醚后处理+PD98059组(EP组)、溶媒DMSO组(D组)。除S组外,均采用大脑中动脉阻闭2h,再灌注24h建立局灶性脑缺血-再灌注模型。缺血2h恢复再灌注即刻,EI组、EP组腹腔注射8%乳化异氟醚10.5ml/kg,其余各组注射生理盐水10.5ml/kg。PD组、EP组和D组于再灌注前30min侧脑室分别注入PD98059和DMSO。再灌注24h时进行神经功能缺陷评分(NDS评分),并观察组织形态学变化及细胞凋亡、p-ERK1/2阳性表达。结果与IR组相比,EI组NDS评分降低,凋亡细胞减少,磷酸化ERK1/2(p-ERK1/2)表达上调(P<0.05);与EI组相比,EP组NDS评分增高,凋亡细胞显著增加,p-ERK1/2表达下调(P<0.05)。结论 8%乳化异氟醚后处理通过激活ERK1/2信号通路对抗局灶性脑缺血-再灌注损伤。

The activation of extracellular signal-regulated kinase 1/2 is involved in the neuroprotection of emulsified isoflurane postconditioning in rats

Objective To observe the effects of extracellular signal-regulated kinase 1/2 (ERK1/2) activation on 8%emulsified isoflurane postconditioning on focal cerebral ischemia-reperfusion in rats.Methods Forty-eight male SD rats were randomly divided into six groups:sham (S) group,ischemia-reperfusion (IR) group,ischemia-repefusion with postcondition of intraperitoneal 8% emulsified isoflurane (EI) group,PD98059 (ERK1/2 inhibitor) intervention (PD) group,emulsified isoflurane plus PD98059 (EP) group and DMSO (D) group.Rats were subjected to the right middle cerebral artery occlusion (MCAO) for 2 h and followed 24 h reperfusion except the rats in group S.Emulsified isoflurane was administered immediately after reperfusion,while PD98059 and DMSO were administered 30 min before reperfusion.Twenty-four hours after reperfusion,neurologic deficit scores (NDS),tissue morphology changes apoptotic index and the positive expression of p-ERK1/2 were evaluated.Results Compared with the IR group,EI group had lower NDS,decreased cell apoptosis,and up-regulated phosphorylated ERK1/2 (p-ERK1/2) expression (P<0.05).Compared with EI group,EP group had higher NDS,increased cell apoptosis and down-regulated p-ERK1/2 expression (P<0.05).Conclusion ERK1/2 activation.is involved in the mechanisms of 8% emulsified isoflurane postconditioning attenuating focal cerebral ischemia-reperfusion injury.