The Efficacy And Possible Mechanisms About Celecoxib(COX-2Inhibitors)as An Adjunctive Treatment For Rats With Refractory Partial Epilepsy

Objective:this study was designed to observe the effect and possible mechanisms about Celecoxib(COX-2inhibitors)as an adjunctive treatment for rats with refractory partial epilepsy,through comparing the differences of therapeutic effect in every groups and the exprssion of cyclooxygenase-2(COX-2) and p-glycoprotein(P-GP). This study would provide a new idea for clinical. Methods:1.Dividing into groups:The experiment set up five experimental groups including sham-operated group,saline treated group, carbamazepine reated group,carbamazepine joint celecoxib treatment group, Celecoxib treatment group.10rats of sham-operated group and12rats of each model groups.2.Building epilepsy models:the rat of refractory epilepsy is builded by using kainic to establish hippocampus kindling ratsand.first, dissolve kainic in nomal saline,according to the dose of1.5ug/200g,density of lug/ul,route of administration is hippocampus injection.At the same time,give equal normal saline to sham-operated group by Hippocampus injection.3. selecting epilepsy models: Carbamazepine orally, once daily, the dosage of125mg/kg for28days, and observed on rat seizures and measured the EEG..4、selecting criteria: a. EEG, observation of rat EEG with or without high amplitude sharp waves, slow waves and other abnormal epileptic; b, in accordance with the Racines hierarchical observation:0:normal;1:wet dogquiver, hemifacial spasm, such as the blink of an eye, moving to be rhythmic chewing;2:rhythmic nodding;3:forelimb spasms;4:standing with bilateral forelimb spasms;5:Continuing to stand or fall on the loss of balance,limbs twitching. Attack to achieve3to5for the exception, c, refractory epilepsy models. Must be both abnormal.5, drug treatments: five experimental groups were given the appropriate drug treatment for28days.6, detection of indicators:the rats attack, EEG, p-glycoprotein and COX-2immunohistochemical detection of experimental results. Results:1, the efficacy of combination therapy:combination therapy for28days, rats seizures and EEG showed that the joint carbamazepine and celecoxib treatment of refractory epilepsy model is better than carbamazepine ((p=0.044, p<0.05) and celecoxib treatment monotherapy (p=0.012, p<0.05).After treating28days on Carbamazepine drug, we studied the correlation of the expression tendency and compared the different expression of P glycoprotein and COX-2in brain tissue and EEG.2、single-drug treatments:the efficacy of the celecoxib treatment group is close to the carbamazepine treatment group and the saline treatment group i(p=0.50, p>0.05).3the effects of Celecoxib on the Expression about COX-2and p-glycoprote in rat brain tissue of refractory epilepsy model:brain tissue COX-2and P-GP in content in the combined treatment group is less that of the saline group (p <0.01) and carbamazepine treatment group (p<0.01). brain tissue COX-2and P-GP in content i in the Celecoxib treatment group is less that of the saline group (p<0.01) and carbamazepine treatment group (p <0.01).4Correlation about the COX-2and p-glycoprotein in rat brain tissue:After28days of treatment, using optical density analysis of p-glycoprotein and the COX-2levels in rat brain tissue, the results show,COX-2in rat brain tissue and p-glycoprotein is linear correlation (r=0.777).5. The relationship between the COX-2expression and treatment effect:The mice were divided into two groups in the carbamazepine treatment group and the combination therapy group in accordance with the COX-2expression. We found that the efficacy of low expression of the COX-2is well to the effects of high expression of COX-2(p=0.025, p<0.05)6.the relationship between the P-GP expression and treatment effect:The rats on the carbamazepine treatment group and the combination therapy group were divided into two groups in in accordance with the P-GP expression.We found that the efficacy of low expression of the COX-2is well to the effects of high expression of P-GP(p=0.028, p<0.05). Conclusions It is reduce that seizures in rats and reduce the COX-2and p-glycoprotein expression on the combination therapy group, which indicates the ralationship between the expression of COX-2and p-glycoprotein and multidrug resistangce. Confirmed that the COX-2inhibitors can decreasing expression of p-glycoprotein.By inhibiting the expression of COX-2, Leading to a reduction in the frequency of seizures...