塞来昔布对大鼠重型颅脑创伤后运动功能及Apaf-1蛋白表达的影响

摘要

目的：探讨在大鼠重型颅脑创伤模型中，塞来昔布对环氧合酶（COX）-2和凋亡蛋白酶活化因子-1（Apaf-1）蛋白表达及运动功能的影响。方法48只成年雄性Wistar大鼠按随机数字表法随机等量分为4组。正常对照组不做任何处理，假手术组给予头皮切开并缝合，损伤组采用Foda法建立大鼠重型闭合性颅脑创伤模型，治疗组在损伤组基础上立即腹腔注入塞来昔布（250 mg/kg，给药间隔6 h/次），其余3组在同等条件下给予等量生理盐水，72 h后统一取材。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。同上述分组方法每组另取6只，经10 d恢复后应用神经功能损害评分（NSS）对大鼠运动功能进行检测。结果损伤组COX-2和Apaf-1蛋白表达水平明显高于其他组，治疗组与损伤组比较能有效降低蛋白表达，但仍高于假手术组和正常组（P<0.05）；NSS评分显示治疗组与损伤组比较能有效改善大鼠的运动功能障碍（P<0.05），但与假手术组和正常对照组比较仍有差距（P<0.05）。结论塞来昔布可通过对COX-2蛋白的特异性抑制，减少由其引发的炎症反应，进一步降低Apaf-1蛋白的表达，从而减少神经细胞的凋亡，并改善大鼠脑创伤后的运动功能障碍。%Objective To investigate effects of celecoxib on the expression of cyclooxygenase-2 (COX-2), apoptotic protease activation factor-1 (Apaf-1) and function of mobility in rat model of severe craniocerebral trauma. Methods For⁃ty-eight adult male Wistar rats were randomly divided by random number table into four groups. Normal group was given no manipulation. Sham group was given scalp incision and sutured. The severe closed craniocerebral injury model was estab⁃lished via Foda method in rats of injury group. Treatment group was given intraperitoneal injection of celecoxib [ 250 mg/(kg·6 h)] on the basis of injury group. The intraperitoneal injection of same volume of normal saline was given in the other three groups. Samples were taken altogether after 72 hours. Changes of COX-2 and Apaf-1 were detected by immunohistochemis⁃try and Western blot assay. Ten days after the restoration, six rats were taken from each group for assessing neurological im⁃pairment scale (NSS). Results The expression levels of COX-2 and Apaf-1 were significantly higher in injury group than those of other groups. The expression levels of COX-2 and Apaf-1 were significantly lower in treatment group than those of injury group but the levels were significantly higher than those of sham group and normal group (P < 0.05). NSS scores showed that rats in treatment group improved mobility compared with that of injury group (P<0.05), but there was difference compared with Sham group and control group (P<0.05). Conclusion Celecoxib, with its specific inhibitoty effect on pro⁃tein COX-2, can effectively reduce inflammatory reactions lower the expression of Apaf-1 and reduce apoptosis of neurons, improving the prognosis of dysfunction of mobility after craniocerebral injury.