阻断孤啡肽受体对大鼠局灶性脑缺血损伤的保护作用

目的 研究侧脑室给予孤啡肽受体(ORL-1)阻断药对大鼠脑缺血-再灌注损伤的影响.方法 雄性SD大鼠55只,随机分为三个不同剂量的给药组(T_1、T_2、T_3组)和假手术组(S组)、对照组(C组),每组11只.给药组和C组都采用线栓法阻断大脑中动脉模型(MCAO),缺血2 h后恢复再灌注.给药组于手术前45 min右侧脑室分别给予ORL-1阻断药Nphel 0.03、0.3、3 nmol,剂量10μl.每组大鼠随机分为两部分,其中8只在恢复再灌后24 h行行为学评分(NDS),后断头取脑行TTC染色,计算脑梗死容积.3只在恢复冉灌注后24 h断头分离右侧海马组织,Western blot法分析Caspase-3蛋白表达.结果 与C组相比,T_3组的NDS明显提高(P<0.05),T_2、T_3组的脑梗死容积明显减小(P<0.05);T_2、T_3组在缺血-再灌注后24 h Caspase-3蛋白表达明显降低.结论 阻断ORL-1能剂量依赖性减轻脑缺血-再灌注损伤.其机制可能与阻断神经元凋亡有关.

The protection of orphanin receptor blockade on focal cerebral ischemia in rats

Objective To investigate the effect of intracerebroventricular administration of orphanin receptor antaonist Nphe on cerebral ischemia-reperfusion(I-R) injury in rats.Methods Fifty-five male SD rats were divided randomly into 5 groups of sham operated (group S,control (group C) ,Nphe 0.03 nmol treated(group T_1) ,0.3 nmol(group T_2) and 3 nmol(group T_3).The I-R model was established by the ligation of middle cerebral artery(MCAO) and reperfused after occlusion for 2 hours in group C and Nphe groups.The rats in Nphe groups were intracerebroventricularly given Nphe at 45 min before MCAO surgery.Of each group,8 rats were taken for behavioral scoring and TTC staining at 24 h after MCAO surgery,and 3 rats for detecting Caspase-3 level in right hippoeampus by Western blot at 24 h after MCAO surgery.Results The behavior scores were higher in group T_2 than those in group C(P<0.05).The volume of cerebral infarction in groups of T_2and T_3 were significantly decreased dose-dependently(P<.(0.05).administration of 0.3 nmol and 3 nmol Nphel significantly decreased Caspase-3 protein expression in the hippocampus after cerebral I-R.Conclusion Orphanin receptor antaonist can attenuate the injury of cerebral I-R dose-dependently,which may be associated with a decrease in neuron apoptosis.