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

Celecoxib down-regulates Apaf-1 protein expression for promoting learning and mem craniocerebral traumaory function recovery after in rats

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72h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72h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 72h-reperfusion was performed for taking brain specimens.The immunohistochemical method and Western blot were used to respectively detect COX-2and Apaf-1protein expression change;the Morris water maze test was adopted to detect the learning and memory function on preoperative 5dand at postoperative 72 h.Results The COX-2and Apaf-1protein 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 4groups（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-2inhibitor celecoxib can downregulate the expression of COX-2and Apaf-1protein,inhibit inflammation reaction and cellular apoptosis,and improve the learning and memory dysfunction after traumatic brain injury.