Effects Of Celecoxib On Expression Of NF-κ Bp65 And PGP In Hippocampus Of Chronic Temporal Lobe Epileptic Rats

ObjectiveTemporal lobe epilepsy (TLE) is one of the main types of intractable epilepsy, whose pathogenesis has not been fully understood. It is a challenge for clinical and fundamental research to treat it more effectively. The kainic acid(KA) induced TLE of rats is established as a model in this study. To observe the effects of cyclooxygenase-2 inhibitor, celecoxib on expression of nuclear factor kappaBp65(NF-KBp65) and p-glycoprotein(PGP) in the hippocampus of rats with chronic TLE, investigate the relationship between NF-κBp65, PGP and the pathogenesis of TLE, and to explore the potential of cyclooxygenase-2 inhibitor as an adjunctive therapy of anti-epileptic drugs.MethodsThirty male SD rats were divided into normal saline(NS) control group, model group and celecoxib treatment group (n=10). TLE model was induced by injection of KA into the CA3 area of hippocampus using a stereotaxic apparatus, while control group was injected equal NS. Eight weeks after status epilepsy(SE), the rats in celecoxib treatment group received intraperitoneal injection of celecoxib (10mg/kg) once daily for 10 days. The expression of NF-KBp65 and PGP in hippocampus of rats was detected by immunohistochemical technique and western blot.Results1. KA induced rats epilepsy model are established. The changes in behavior experienced three phases, which were acute, silent and chronic. The rate of successful SE model was 85.2% and mortality was 25.9%.All the surviving SE rats were induced to spontaneous epilepsy and recurrence of symptoms two weeks after SE. The rate of successful chronic model was 74.1%.2. NF-KBp65 and PGP in the hippocampus was detected in normal saline control group, model group and celecoxib treatment group respectively using immunohistochemistry technique. The results showed:1) NF-κBp65 was slightly expressed in normal saline control group. Compared with normal saline control group, NF-KBp65 nuclear translocation in hippocampus of rats with TLE increased significantly (P<0.05).Celecoxib administration prevented NF-κBp65 translocation into nucleus in the hippocampus of TLE rats significantly (P<0.05).2) In normal control group PGP positive neuron can not be found in hippocampus. In model group the number of PGP positive neuron in hippocampus increased significantly. Celecoxib administration down-regulated the expression of PGP in the hippocampus of TLE rats significantly (P<0.05).3. NF-KBp65 and PGP in the hippocampus was detected in normal saline control group, model group and celecoxib treatment group respectively using western blot experiments. The results showed:1) NF-KBp65 was slightly expressed in normal saline control group. Compared with normal saline control rats, the expression of NF-KBp65 in the hippocampus of rats with TLE increased significantly (P<0.05) Celecoxib administration down-regulated the expression of NF-KBp65 in the hippocampus of TLE rats significantly (P<0.05).2) PGP was slightly expressed in normal saline control group. Compared with normal saline control rats, the expression of PGP in hippocampus of rats with TLE increased significantly (P<0.05). Celecoxib administration down-regulated the expression of PGP in the hippocampus of TLE rats significantly(P<0.05).Conclusion1 The chronic temporal lobe epileptic rat model induced by injection of KA was an ideal animal model to simulate human TLE, and it could be used for the reseach.2 The increase in NF-κBp65 and PGP expression and NF-KBp65 nuclear translocation during chronic epilepsy period may participate in the pathogenesis of TLE.3 The administration of celecoxib may be provide anti-epilepsy against inflammatory response and multi-drug resistance.4 Cyclooxygenase-2 inhibitor as an adjunctive therapy of anti-epileptic drugs may be provide a new method.