抗癫痫药耐药性鼠模型的建立及其P-gp的表达

目的：建立抗癫痫药（AED）耐药性大鼠模型，并观察其P-糖蛋白（P—gp）的表达。方法：首先应用氯化锂一匹罗卡品诱导癫痫鼠模型，然后在此基础上进一步用苯妥英钠药物筛选的方法获得AED的耐药性大鼠模型。通过RT-PCR、蛋白印迹法（Western Blot）和免疫组化等方法研究P—gP在该动物模型脑内不同部位的表达。结果：应用氯化锂一匹罗卡品诱导的癫痫鼠模型进行药物筛选的方法成功获得了AED耐药性癫痫动物模型，并经临床评分和脑电图证实。耐药性癫痫模型大鼠海马、小脑及大脑皮层的P—gP表达水平均显著高于非耐药性癫痫大鼠及正常对照大鼠。结论：对氯化锂一匹罗卡品诱导的鼠模型进行药物筛选的方法可建立AED耐药性癫痫动物模型；P—gP在AED耐药性癫痫大鼠脑内表达水平显著升高。

Estabilishment of antiepileptic drug resistant model and its P-gp expression in rats

Objective：To establish the antiepileptic drug-resistan model and to observe the expression of P-glycoprotein（P-gp）in rats. Methods： The epileptic rat model were first with lithium chloride-pilocarpine to induce epilepsy in rats. Then the antiepileptic drug resistant model were screened out with phenytoin from established rat models. RT-PCR, Western Blot and immunohistochemical staining was carried out to present expression of P-gp in different loci of the rat brains. Results： It was identified by clinical scoring and EEG that the pbarmaoresistantl（or refractory） epilepstic models were successfully established with this method. The P-gp expressions in the hipocampus, cerebellum and cortex were all higher in refractory epileptic rats than those in the normal and non-refractory rats. Conclusions： Lithiumpilocarpine and drug-screening can be used to produce the refractory epilepsy models. The expression of P-gp in refractory epilepsy model rats is heightened significantly.