天津医药

天津医药 ›› 2016, Vol. 44 ›› Issue (6): 716-719.doi: 10.11958/20150231

• 实验研究 • 上一篇    下一篇

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

张涛 1， 国建飞 1， 邢琳琳 1， 张金玲 2， 张宇新 3   

  1. 1河北医科大学附属邢台人民医院 （邮编054031）； 2邢台医学高等专科学校； 3华北理工大学医学院
  • 收稿日期:2015-10-15 修回日期:2016-01-06 出版日期:2016-06-15 发布日期:2016-07-04
  • 基金资助:
    河北省自然科学基金项目（C2004000689）； 河北省博士基金项目（05547008D-4）； 河北省科学技术与社会发展计划项目（04276135）

Effects of celecoxib on expression of protein Apaf-1 and function of mobility after severe craniocerebral injury in rats

ZHANG Tao1, GUO Jianfei1, XING Linlin1, ZHANG Jinling2, ZHANG Yuxin3   

  1. 1 The Affiliated Xingtai People′s Hospital of Hebei Medical University, Xingtai 054031, China; 2 Xingtai Medical College; 3 Medical College of North China Institute of Technology
  • Received:2015-10-15 Revised:2016-01-06 Published:2016-06-15 Online:2016-07-04

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摘要： 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。

关键词: 颅脑损伤, 环氧化酶 2, 凋亡蛋白酶活化因子 1, 神经功能损害评分

Abstract: Abstract： 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.

Key words: craniocerebral trauma, cyclooxygenase 2, apoptotic protease- activating factor 1, neurological severity scores