塞来昔布对颅脑损伤后生成素表达及神经元凋亡的影响  

Effects of celecoxib on the expression of Survivin and neuron apoptosis after traumatic brain injury in rats

作　　者：张金玲[1] 张涛 国建飞 郑丽[1] 杨群福 崔福生 张宇新 

机构地区：[1]邢台医学高等专科学校药学系,河北邢台054031 [2]河北医科大学附属邢台市人民医院神经外科,河北邢台054031 [3]华北理工大学基础医学院,河北唐山063000

出　　处：《中国临床药理学杂志》2017年第24期2592-2594,2602,共4页The Chinese Journal of Clinical Pharmacology

基　　金：河北省自然科学基金资助项目(C2004000689);河北省博士基金资助项目(05547008D-4);河北省科学技术与社会发展计划基金资助项目(04276135)

摘　　要：目的研究塞来昔布对大鼠颅脑创伤后Survivin表达及神经元凋亡的影响。方法按照体重将SD大鼠随机分为4组:正常组、假手术组、模型组、实验组,每组16只。实验组在大鼠闭合性颅脑创伤模型构建后,立即经腹腔注入塞来昔布250 mg·kg^(-1),给药间隔每次6 h;正常组、假手术组和模型组给于同等量的0.9%NaCl腹腔注射。用免疫组织化学法检测Survivin和半胱氨酸天冬氨酸蛋白酶-3(Caspase-3)蛋白表达;以原位末端标记技术(TUNEL)检测神经细胞凋亡情况。结果正常组、假手术组、模型组和实验组的Survivin蛋白表达量分别为3.19±1.43,5.34±1.26,14.17±0.54,27.76±0.70;这4组的Casepse-3蛋白表达量分别为1.19±0.51,3.19±0.71,11.17±3.74,6.30±2.80。与正常组和假手术组比较,模型组差异均有统计学意义(均P<0.05);与模型组比较,实验组差异均有统计学意义(均P<0.05)。在6,12,24,72 h的凋亡细胞数:假手术组、模型组和实验组分别为2.84±0.56,12.17±1.74,5.36±0.80;3.19±0.71,33.17±3.74,26.30±2.80;5.34±0.83,72.57±6.74,58.48±4.50;2.44±0.83,61.28±5.36,42.56±4.63。与假手术组比较,模型组差异均有统计学意义(均P<0.05);与模型组比较,实验组差异均有统计学意义(均P<0.05)。结论塞来昔布可能通过增加抗凋亡蛋白Survivin表达来抑制Caspase-3激活介导的凋亡程序,以减少颅脑创伤后神经细胞凋亡,发挥颅脑保护作用。Objectve To investigate the effect of celecoxib on the expre- ssion of Survivin and neuronal apoptosis after traumatic brain injury in rats, and to explore its brain protection mechanism. Methods The 64 SD rats were randomly divided into four groups： normal group, sham operation group, model group and experimental group. The rats in experi- mental group and model group were established with closed craniocerebral injury model by free falling method. In the experimental group, intraperitoneal injection of celecoxib （250 mg · kg ^- 1 ） was performed im- mediately after the craniocerebral injury model was established. The rats in sham operation group and the normal group were given the same amount of 0. 9% NaCl intraperitoneally. The expressions of Survivin and Caspase- 3 were detected by immunohistochemistry. The neuronal apoptosis was detected by TdT- mediated dUTP- biotin nick endlabeling（TUNEL） method. Results The expression of Survivin protein in the normal group, sham- operated group, model group, and experimental group were 3.19 ±1.43,5.34 ± 1.26,14. 17 ±0. 54,27.76 ± 0. 70. The expression of Casepse -3 protein in above four groups were 1.19 ±0. 51,3.19 ±0, 71,11.17 ±3.74,6. 30±2. 80. The expression of Survivin in the model group was significantly higher than in normal group and sham - operated group with significantly （ all P 〈 0. 05 ）. Compared with the model group, the expression of Survivin and Caspase - 3 in the experimental group increased with significantly （ all P 〈 0. 05 ）. The number of apoptotic cells in 6,12,24,72 h in the sham - operated group, model group, and experimental group were 2.84 ± 0.56, 12. 17 ± 1.74, 5.36 ±0.80;3.19 ± 0.71, 33.17 ± 3.74, 26. 30 ± 2. 80;5.34 ± 0. 83,72.57 ± 6. 74,58.48 ± 4. 50;2. 44 ± 0.83,61.28 ±5.36,42.56 ± 4. 63. The number of apoptotic cells in the model group was significantly higher than in sham - operated group with significantly （ all P 〈 0. 05 ）. Compared with the model group, the number of apoptotie cells in the

关 键 词：塞来昔布 生存素 半胱氨酸天冬氨酸蛋白酶-3 颅脑损伤 神经元凋亡 

分 类 号：R982[医药卫生—药品]