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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

张涛   

  1. 河北医科大学附属邢台市人民医院
  • 收稿日期:2011-09-21 修回日期:2011-12-26 出版日期:2012-06-15 发布日期:2012-06-15
  • 通讯作者: 张涛

The Effect of the Celecoxib on memory function and the expression of Caspase-3 protein after traumatic brain injury .

  • Received:2011-09-21 Revised:2011-12-26 Published:2012-06-15 Online:2012-06-15

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摘要： 目的 在分子生物学水平进一步研究颅脑创伤后炎症反应变化,探讨选择性环氧合酶(COX-2)抑制剂塞来昔布对大鼠重型颅脑创伤后学习记忆功能及Caspase-3蛋白表达的影响。方法 采用Marmarou 的方法建立大鼠重型闭合性颅脑创伤模型, 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、正常对照组,各组均在相应的时间点处死取材，应用免疫印迹Western blot方法及免疫组化法检测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 脑创伤后大鼠脑内COX-2及Caspase- 3蛋白表达增加，塞来昔布治疗组COX-2 及Caspase- 3蛋白表达高峰明显下调,与脑创伤组相比有统计学意义（p＜0.05）,伤后第9、10天水迷宫测试的潜伏期明显缩短，与脑创伤组相比有统计学意义（p＜0.01）。结论 COX-2 抑制剂塞来昔布对大鼠重型颅脑创伤有脑保护作用，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,能够改善其伤后学习记忆障碍。

关键词: 颅脑损伤, COX-2, Caspase-, 塞来昔布, Morris水迷宫

Abstract: Objective This is a study on the level of molecular biology to clarify the change regulation of inflammatory reaction and to investigate the effect of cyclooxygenase -2 inhibitor Celecoxib on memory function and the expression of Caspase-3 protein after traumatic brain injury (TBI) .Methods The model of severe closed TBI was established according to the method created by Marmarou. Adult Wistar rats (n=48) were randomly divided into TBI group , Celecoxib treatment group , sham operation group, normal controls. All rats were killed at each time point ,for detective COX-2 and Caspase-3 protein expression with West-blot and immunohistochemistry. Another 24 rats were randomly divided into TBI group , Celecoxib treatment group , sham operation group , and normal group . The cognitive dysfunction was evaluated using the Morris water maze (MWM) . Results The increased expression of protein COX-2 and Caspase-3 in brain after TBI, Celecoxib can apparently decrease COX-2 and Caspase-3 protein expression in brain, Celecoxib treatment group is compare with TBI group in distinction bears significance in statistics（p＜0.05）, and it can obviously shorten the latency of Morris water maze tests in 9、10day,the distinction bears have a significance in statistics（p＜0.01）.Conclusion Celecoxib can apparently decrease the expression of COX-2 and caspase-3, and inhibition of inflammatory reaction and apoptosis ，obviously shorten the latency of Morris water maze tests.

Key words: traumatic brain injury, COX-2 , Caspase-3 , Celecoxib , Morris water Maze