帕瑞昔布减轻大鼠全脑缺血所致海马CA1区神经元损伤

Parecoxib protectives hippocampal CA1 neurons from global cerebral ischemic damage by activating microglia

目的探讨COX-2抑制剂帕瑞昔布对大鼠全脑缺血模型海马CA1区损伤神经元的影响及潜在小胶质细胞激活和保护神经元的机制。方法 SPF级健康大鼠30只,体重200~250g,采用随机数字表法分为三组:假手术组、缺血-再灌注组和帕瑞昔布组,每组10只。用四血管闭塞法制作大鼠全脑缺血模型。手术完成30min后,帕瑞昔布组给予帕瑞昔布腹腔注射10mg/kg,其余两组给予等体积生理盐水0.5ml,连续给药3d,第7天进行水迷宫实验,结束后灌注固定取脑,石蜡切片后进行Nissl染色,观察海马CA1区存活神经元的数量,然后进行免疫荧光染色,观察海马区小胶质细胞形态学变化。结果与假手术组比较,缺血-再灌注组海马CA1区神经元受损明显,大量神经元发生凋亡,大鼠的学习记忆能力明显降低(P<0.05),海马区小胶质细胞被激活;与缺血-再灌注组比较,帕瑞昔布组海马CA1区神经元状态明显好转,存活神经元数量明显增加,大鼠的学习记忆能力明显改善(P<0.05),海马区小胶质细胞形态上呈现激活状态,部分小胶质细胞胞体有阿米巴样变化。结论帕瑞昔布对因缺血损伤导致的学习记忆能力下降有明显的改善作用,这种作用可能与小胶质细胞被激活或功能状态发生改变有关。

Objective To investigate the effect of COX-2 inhibitor parecoxib on neurons in hippocampal CA1 of rats after global cerebral ischemia and explore roles of microglia activation.Methods A total of 30 SPF healthy rats,weighing 200-250 g,were randomly divided into three groups：sham group,control group,and parecoxib group,10 rats in each.30 minutes after four vessel occlusion operations,parecoxib group received parecoxib 10 mg/kg treatment intraperitoneally,the other two groups were given saline,administered continuously for 3 days.On the 7 th day,water maze tests were proceeded,then the rat brains were perfusion fixed.After paraffin sectioning and Nissl staining and immunofluorescence staining,the numbers of survival neurons in hippocampal CA1 region were quantified and the morphologic changes of microglia were observed.Results Compared with sham group,the hippocampal CA1 neurons of control group were significantly damaged,large numbers of neurons were in apoptosis,the learning and memory ability of rats was significantly decreased（P〈0.05）,hippocampus microglial cells were activated.Compared with control group,neuron numbers in hippocampal CA1 area of parecoxib group were significantly increased,water maze test also showed significantly improved learning and memory ability（P〈0.05）,hippocampal microglial cells were activated to a much greater level.Conclusion COX-2 inhibitor parecoxib significantly rescues hippocampal neurons from ischemic damage and improves the learning and memory ability after ischemic injury,which might be closely related to the activation of microglia.