Abstract: 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 cyclooxygenase-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 hippocampus using a stereotaxic 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-κ Bp65 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-κ Bp65 and P-gp, and prevented NF-κ Bp65 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 celecoxib may provide anti-epilepsy against inflammatory response and multi-drug resistance.

Key words: Epilepsy, temporal lobe, Cyclooxygenase inhibitors, NF-kappa B, P-glycoproteins, Drug tolerance, Immunohistochemistry, Disease models, animal

摘要： 目的 探讨环氧合酶-2抑制药塞来昔布对慢性颞叶癫痫大鼠海马核因子-κBp65和P-糖蛋白表达的影响，以及核因子-κBp65和P-糖蛋白与颞叶癫痫发病机制的关系，以为环氧合酶-2抑制药用于抗癫痫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痫动物模型，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，颞叶癫痫大鼠海马核因子-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-糖蛋白在颞叶癫痫慢性期表达上调、核因子-κBp65 核移位现象增加，有可能是难治性癫痫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痫大鼠海马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痫作用。

关键词: 癫痫, 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