大鼠重型颅脑创伤后COX-2蛋白表达对学习记忆功能的影响

Effect of COX-2 protein expression on learning and memory function after severe traumatic brain injury in rats

目的:观察大鼠重型颅脑创伤后COX-2的表达及选择性COX-2抑制剂NS-398对大鼠重型颅脑创伤后学习记忆功能的影响.方法:采用Marmarous方法建立大鼠重型闭合性颅脑创伤模型,将成年Wistar大鼠360只随机分为脑创伤组、NS-398治疗组、假手术组,每组又分为伤后1,3,6,12,24,48,72,96,168及336h10个时相组,另取120只作为正常对照组.NS-398治疗组经致伤后,给予腹腔注射NS-39840mg/(kg.d),直至各时相点处死;脑创伤组、假手术组及正常对照组在相同时间给予等量的生理盐水腹腔注射.各组均在相应的时间点处死取材应用WesternBlot方法及免疫组化法检测COX-2蛋白变化.再取24只大鼠随机分为脑创伤组、NS-398治疗组、假手术组及正常对照组,进行水迷宫测试.结果:NS-398能够使大鼠脑内COX-2蛋白表达高峰明显下调,使水迷宫测试的潜伏期明显缩短.结论:提示COX-2与脑创伤后引发的继发性脑损伤密切相关,NS-398能够明显改善大鼠重型颅脑创伤后学习记忆障碍.

AIM： To observe the expression of COX-2 and the effect of the selective COX-2 inhibitor NS-398 on learning and memory function of rats 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 = 360） were randomly divided into TBI group, NS-398 treatment group, and sham operation group, and each of them was sub-divided into post-traumatic 1, 3, 6, 12, 24, 48, 72, 96, 168 and 336 h groups. Another 120 rats were taken as normal controls. The NS-398 treatment group after injury was treated with NS-398 [40 rag/ （kg·d） ]ip. The TBI group, the sham operation group, and the control group were treated with normal saline. All rats were killed at each time point, for detecting COX-2 protein expression with Western Blot and immunohistochemistry. Another 24 rats were randomly divided into TBI group, NS-398 treatment group, sham operation group, and normal group. The cognitive dysfunction was evaluated using the Morris water maze （MWM）. RESULTS： NS-398 could apparently down-regulate the peak of COX-2 protein expression in brain and obviously shorten the latency of Morris water maze tests. CONCLUSION： COX-2 is correlated with secondary brain injury induced by TBI, and NS-398 may effectively improve cognitive dysfunction after TBI.