依托咪酯后处理对大鼠脑缺血再灌注损伤脑细胞凋亡及Fas/Fasl蛋白表达的影响

目的探讨依托咪酯后处理对大鼠脑缺血再灌注损伤脑细胞凋亡及fas/fasl蛋白表达的影响。方法健康Wistar大鼠40只,体重200-250g,随机分为假手术组（SH组）、缺血再灌注组（I/R组）、依托咪酯后处理组（E1、E2、E3组）五组。I/R组和E1、E2、E3组夹闭双侧颈总动脉制备脑缺血模型,SH组只暴露双侧颈总动脉。E1、E2、E3组分别于缺血20min、再灌注前3min经股静脉给予依托咪酯0.3mg、0.9mg、2.7mg/kg,I/R组和SH组给予等量生理盐水。五组均于再灌注24h处死,断头取脑组织切片,HE染色法光镜下观察脑组织形态学变化,TUNEL法检测脑细胞凋亡,免疫组化法测定fas/fasl蛋白表达。结果与SH组比较I/R组和E1、E2、E3组脑细胞凋亡指数（AI）升高,Fas/Fasl蛋白表达上调（P均〈0.01）。与I/R组比较E1、E2、E3组AI降低,Fas/Fasl蛋白表达下调（P均〈0.01）。E1、E2与E3组比较,AI降低,Fas/Fasl蛋白表达下调（P均〈0.01）结论依托咪酯后处理可以降低脑缺血再灌注损伤脑细胞凋亡以及fas/fasl蛋白表达,其作用以中、小剂量较为显著。

Effects of Etomidate postconditioning on apoptosisi and expression of Fas/Fasl in rats following ischemia-reperfusion

Objective To investigate the Effects of Etomidate postconditioning on apoptosis and expression of Fas/Fasl in rats following ischemia-reperfusion.Methods 40 Wistar rats were randomly devided into 5 groups: the sham group(SH n=8),the ischemi reperfueion group(I/Rn=8),and three postconditioning groups of ETO(E1,E2,E3).in group IR and group ETO(E1,E2,E3) the rats wre subjected to ischemia by clipping of bilateral common carotid arteries.Group SH only exposuring CCA.At 23 minutes before reperfusion E1-3 groups with different dose of ETO(0.3mg/kg,0.9mg/kg,2.7mg/kg),IR group and SH group with 1ml normal saline by femoral vein injection.After the reperfusion period of 24h,the rats were sacrificed.The number of apoptosis neuron were observed by Tunel method and the expression of fas/fasl were detected by immunochemistry method.Result Compared with SH group the mean gradation of fas/fasl in E1-3 groups and IR group significantly decreased,Tunel positive cells sigmificantly increased,in contrast both E1 and E2 group showed lower level of apoptosis,the expression of fas/fasl protein decreased.Conlusion The effect of ETO postconditioning can inhibit neuron apoptosis of ischemic and reduce the expression of fas/fasl protein,which may be one of mechanisms of neuroprotective effects of ligustrazine.