ERK1/2激活参与乳化异氟醚后处理的脑保护作用

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

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。

Objective To observe the effects of extracellular signal-regulated kinase 1/2 （ERK1/2） activation on 8% emulsified isoflurane postconditioning on focal cerebral ischemiareperfusion 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 （El） 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. Resulls Compared with the IR group, El 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）. Condmion ERK1/2 activation, is involved in the mechanisms of 8% emulsified isoflurane postconditioning attenuating focal cerebral ischemia-reperfusion injury.