塞来昔布对慢性颞叶癫癎大鼠海马核因子-κBp65和P-糖蛋白表达的影响  

Effects of celecoxib on expression of NF-KBp65 and P-gp in hippocampus of chronic temporal lobe epileptic rats

作　　者：张秀娜[1] 武士京[1] 陶华英[2] 张丽娜[3] 

机构地区：[1]天津医科大学总医院神经内科,300052 [2]天津市神经病学研究所神经生理室 [3]河北医科大学第一医院神经内科

出　　处：《中国现代神经疾病杂志》2011年第2期236-241,共6页Chinese Journal of Contemporary Neurology and Neurosurgery

摘　　要：目的探讨环氧合酶-2抑制药塞来昔布对慢性颞叶癫癎大鼠海马核因子-κBp65和P-糖蛋白表达的影响,以及核因子-κBp65和P-糖蛋白与颞叶癫癎发病机制的关系,以为环氧合酶-2抑制药用于抗癫癎药物辅助治疗提供实验依据。方法采用大鼠海马CA3区微量注射海人酸的方法制备颞叶癫癎动物模型,免疫组织化学染色和Western blotting法观察塞来昔布治疗后大鼠海马核因子-κBp65和P-糖蛋白表达变化。结果与对照组相比较,颞叶癫癎大鼠海马核因子-κBp65、P-糖蛋白表达水平,以及核因子-κBp65核移位现象明显增加(均P<0.05);经塞来昔布治疗后,海马组织中核因子-κBp65、P-糖蛋白表达水平及核因子-κBp65核移位现象显著改善,与模型组比较差异有统计学意义(均P<0.05)。结论核因子-κBp65和P-糖蛋白在颞叶癫癎慢性期表达上调、核因子-κBp65核移位现象增加,有可能是难治性癫癎发生与发展的分子生物学机制之一。环氧合酶-2抑制药塞来昔布通过降低慢性颞叶癫癎大鼠海马CA3区核因子-κBp65和P-糖蛋白表达水平,抑制核因子-κBp65核移位,最终降低炎性反应,逆转多药耐药而发挥抗癫癎作用。Objective To observe the effects of cyclooxygenase-2 inhibitor, celecoxib on expression of nuclear factor-κBp65 （NF-κBp65） and P-glycoprotein （P-gp） in the hippocampus of rats with chronic temporal lobe epilepsy （TLE）, to investigate the relationship between NF-κBp65, P-gp and the pathogenesis of TLE, and to explore the potential of eyelooxygenase-2 inhibitor as an adjunctive therapy of anti-epileptic drug. Methods Thirty male Sprague-Dawley （SD） rats were divided into normal saline control group, TLE model group and celecoxib treatment group （n = 10 in each group）. TLE model was induced by injection of kainic acid into the CA3 area of hippoeampus using a stereotaxie apparatus. Eight weeks after status epilepticus, the rats in celecoxib treatment group received intraperitoneal injection of celecoxib （10 mg/kg） once daily for 10 d. The expression of NF-κBp65 and P-gp in hippocampus of rats was detected by immunohistochemical technique and Western blotting. Results Compared with normal saline control rats, the expression of NF-κBp65 and P-gp, and NF-κBp65 nuclear translocation in hippocampus of rats with TLE increased significantly （P 〈 0.05, for all）. Celecoxib administration down-regulated the expression of NF- KBp65 and P-gp, and prevented NF-κBp65 translocation into nucleus in the hippocampus of TLE rats significantly （P 〈 0.05, for all）. Conclusion These findings suggest that the pathogenesis of TLE is accompanied by an increase in NF-κBp65 and P-gp expression and NF-κBp65 nuclear translocation during chronic epilepsy period, and the administration of eelecoxib may provide anti-epilepsy against inflammatory response and muhi-drug resistance.

关 键 词：癫痼 颞叶 环加氧酶抑制药 NF-κB P糖蛋白类 药物耐受性 免疫组织化 学 疾病模型 动物 

分 类 号：R742.1[医药卫生—神经病学与精神病学]