塞来昔布对颅脑创伤后学习记忆功能及Caspase-3蛋白表达的影响

The Effect of Celecoxib on Memory Function and Expression of Caspase-3 Protein following Traumatic Brain Injury in Rats

目的:探讨选择性环氧合酶-2(COX-2)抑制剂塞来昔布对重型颅脑创伤大鼠脑组织中COX-2和半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)蛋白表达及学习记忆功能的影响。方法:将成年Wistar大鼠48只随机分为脑创伤组、塞来昔布治疗组、假手术组和正常对照组,每组12只。建立大鼠重型闭合性颅脑创伤模型,各组均在相应的时间点处死取材,应用免疫组化法和Westernblot法检测COX-2及Caspase-3蛋白表达。再取24只大鼠随机分为脑创伤组、塞来昔布治疗组、假手术组及正常对照组,进行水迷宫测试。结果:脑创伤组COX-2及Caspase-3的水平高于正常对照组及假手术组,塞来昔布治疗组的COX-2及Caspase-3水平低于脑创伤组,差异有统计学意义(P<0.05)。脑创伤组大鼠脑创伤后7～10d搜索平台所需的时间均大于其他3组,差异有统计学意义(P<0.05),其他3组间比较差异无统计学意义(P>0.05)。结论:塞来昔布对大鼠重型颅脑创伤有脑保护作用,其可降低COX-2、Caspase-3的表达,抑制脑损伤后的炎症反应和细胞凋亡,能够改善脑创伤后的学习记忆障碍。

Objective： To investigate the effect of cyclooxygenase-2 （COX-2） inhibitor celecoxib on the memory func- tion, the expression of COX-2 and caspase-3 following traumatic brain injury （TBI） in rats. Methods： Forty-eight Wistar rats were randomly divided into TBI group, celecoxib treatment group, sham operation group and normal control group （12 for each group）. The rat model of severe closed TBI was established according to the method created by Marmarou. All rats were killed at different time points for detection of COX-2 and Caspase-3 protein expression by Western-blot and immunohistochemis- try. Another 24 rats were randomly divided into TBI group, Celecoxib treatment group, sham operation group and normal con- trol group for evaluation of cognitive dysfunction using the Morris water maze （MWM）. Results： The protein levels of COX-2 and caspase-3 were significantly higher in TBI group than those of sham operation group and normal control group. The pro- tein levels of COX-2 and caspase-3 were significantly lower in Celecoxib treatment group than those of TBI group （P 〈 0.05）. Results of MWM showed that the time to search the platform was significantly extended in TBI group than that of Celecoxib treatment group, sham operation group and normal control group （P 〈 0. 05）, but the difference was no significance between the three groups （P 〉 0.05）. Conclusion： Celecoxib has protective effect on TBI in rats, which may apparently decrease the expression of COX-2 and Caspase-3, inhibit inflammatory reaction and apoptosis and improve the memory function after trau- matic brain injury.