塞来昔布下调Apaf-1蛋白表达促进大鼠颅脑损伤后学习记忆功能恢复的研究

摘要

目的 探讨塞来昔布对大鼠创伤性脑损伤后学习记忆功能和环氧化酶(COX-2)及凋亡蛋白酶活化因子-1(Apaf-1)蛋白表达的影响.方法 将72只成年雄性Wistar大鼠等量分为对照组、假手术组、损伤组和治疗组,术后72 h灌注取脑,应用免疫组化法和Western blot法分别检测COX-2及Apaf-1蛋白表达变化;术前5d和术后72 h采用Morris水迷宫实验观察大鼠学习记忆功能.结果 损伤组COX-2和Apaf-1蛋白表达明显高于其他组,治疗组与损伤组比较蛋白表达均下降(P＜0.05),但仍高于假手术组和对照组(P＜0.05);Morris水迷宫实验中,损伤组逃避潜伏期时间延长为4组之最(P＜0.05),治疗组较损伤组时间有所缩短(P＜0.05).结论 COX-2抑制剂塞来昔布可下调COX-2和Apaf-1蛋白表达,抑制炎性反应、细胞凋亡,改善脑损伤后的学习、记忆障碍.%Objective To study the effect of celecoxib on learning and memory function,cyclooxygenase(COX-2) and the apoptotic protease-activating factor-1(Apaf-1) protein expression after traumatic brain injury in rat.Methods A total of 72 adult male Wistar rats were equally and randomly divided into the normal control group,sham operation group,trauma group and Celecoxib treatment group.Postoperative 72 h-reperfusion was performed for taking brain specimens.The immunohistochemical method and Western blot were used to respectively detect COX-2 and Apaf-1 protein expression change;the Morris water maze test was adopted to detect the learning and memory function on preoperative 5 d and at postoperative 72 h.Results The COX-2 and Apaf-1 protein expression in the trauma group was significantly higher than that in other groups (P＜0.05),and the protein expression in the treatment group and trauma group was decreased,but still higher than that in the sham operation group and normal group(P＜ 0.05);in the Morris water maze test,the prolongation of escape latency time in the trauma group was maximal among 4 groups (P ＜0.05),but the treatment group had a shorter time compared with the trauma group (P＜0.05).Conclusion Craniocerebral trauma can cause different degrees of learning and memory dysfunction,and COX-2 inhibitor celecoxib can downregulate the expression of COX-2 and Apaf-1 protein,inhibit inflammation reaction and cellular apoptosis,and improve the learning and memory dysfunction after traumatic brain injury.