Effects of celecoxib on expression of NF⁃κBp65 and P⁃gp in hippocampus of chronic temporal lobe epileptic rats

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.

DOI：10.3969/j.issn.1672-6731.2011.02.022