帕瑞昔布钠对大鼠局灶性脑缺血再灌注损伤的影响

Effect of parecoxib on focal cerebral ischemia/reperfusion injury in rats

目的 评价帕瑞昔布钠对大鼠局灶性脑缺血再灌注损伤的影响.方法 雄性SD大鼠54只,体重300～350 g,随机分为3组（n=18）：假手术组（S组）、缺血再灌注组（I/R组）和帕瑞昔布钠组（P组）.I/R组和P组采用电凝左侧大脑中动脉、夹闭双侧颈总动脉60 min时进行再灌注的方法制备脑缺血再灌注模型.P组分别于缺血前15 min和再灌注11 h时静脉注射帕瑞昔布钠4 mg/kg,S组和I/R组给予等容量生理盐水.再灌注72 h时进行神经功能评分,然后取脑组织,测定脑梗死体积、肿瘤坏死因子-α（TNF-α）及脑源性神经营养因子（BDNF）表达水平.结果 与S组比较,I/R组神经功能评分降低,脑梗死体积扩大,TNF-α和BDNF表达上调（P＜0.05）;与I/R组比较,P组神经功能评分升高,脑梗死体积缩小,TNF-α表达下调,BDNF表达上调（P＜0.05）.结论帕瑞昔布钠可减轻大鼠局灶性脑缺血再灌注损伤,其机制与抑制炎性反应和上调BDNF表达有关.

Objective To evaluate the effect of parecoxib on focal cerebral ischemia/reperfusion （I/R）injury in rats. Methods Fifty-four male SD rats were randomly divided into 3 groups （ n = 18 each）： sham operatin group （group S）, group I/R and parecoxib group （group P）. The left middle cerebral artery was permanently occluded by bipolar electrical coagulation and both commom carotid arteries were occluded with miniature clips for 60 min followed by reperfusion. Group P received parecoxib 4 mg/kg intravenously 15 min before ischemia and again at 11 h during reperfusion, while group S and I/R received the equal volume of normal saline instead. The neurologic scores were evaluated at 72 h of reperfusion and then the rats were decapitated. Brains were rapidly removed for determination of the infarct volume and expression of TNF-α and brain-derived neurotrophic factor （ BD-NF） .Results The neurologic scores were significantly lower, and the infarct volume was significantly larger, and the expression of TNF-α and BDNF was significantly higher in group I/R than in group S （P 〈 0.05）. The neurologic scores and BDNF expression were significantly higher, the infarct volume was significantly smaller, and TNF-α expression was significantly lower in group P than in group I/R （ P 〈 0.05 ）. Conclusion Parecoxib can reduce focal cerebral I/R injury in rats, and the mechanism may be associated with the inhibition of inflammatory reaction and up-regulation of BDNF expression.