维拉帕米对难治性癫大鼠的疗效及海马P-糖蛋白表达的影响

Effects of Verapamil on Refractory Epilepsy and on Expression of P-glycoprotein in the Hippocampus in Rat Model

目的:观察耐药蛋白抑制剂维拉帕米对难治性癫大鼠的疗效及海马P-糖蛋白表达的影响。方法:Wistar大鼠50只,随机分为生理盐水组(NS组)、匹罗卡品组(PILO组)、卡马西平组(CBZ组)、低剂量维拉帕米组(LDV组)和高剂量维拉帕米组(HDV组),氯化锂-匹罗卡品腹腔注射制作大鼠自发性癫模型,选择耐药癫大鼠,分别给予常规或添加维拉帕米抗癫治疗,观察大鼠性发作频率及海马P-糖蛋白表达的变化。结果:与NS组相比,其它4组大鼠性发作频率增高,海马P-糖蛋白表达增强(P<0.05);LDV组和HDV组大鼠的性发作频率及海马P-糖蛋白表达较PILO组和CBZ组降低(P<0.05);PILO组和CBZ组大鼠性发作频率及海马P-糖蛋白表达无明显差异,LDV组和HDV组大鼠性发作频率及海马P-糖蛋白表达无明显差异。结论:添加维拉帕米治疗可明显减少难治性癫大鼠性发作频率,降低难治性癫大鼠海马P-糖蛋白的表达。

Objective： To investigate the therapeutic effect of verapamil on refractory epilepsy and the effect of vrerapmil on expression of P-glycoprotein （P-gp） in the hippocampus in rat model of refractory epilepsy. Method： A rat model of spontaneous recurrent seizures （SRS） has been generated through lithium-pilocarpine lumbar injection. The SRS rats with drug resistance were selected and randomly divided into the control, the pilocarpine, the earbamazepine, the low-dose verapamil and the high-dose verapamil group. The frequency of SRS and the expression of P- gp in hippocampus of rats have been documented. Results： The frequency of SRS and the expression of P-gp in hippocampus in the control group were significantly lower than that in the other four groups （P〈0.05）. The frequency of SRS and the expression of P-gp in hippocampus in both the low-dose and the high-dose verapamil groups were significantly lower than those in the carbamazepine and the pilocarpine groups （P〈0. 05）. There was no differences between the earbamazepine group and the pilocarpine group and no difference between the low-dose and the high- dose verapamil group either. Conclusion： Treatment of verapamil may significantly decrease the frequency of SRS and lower the expression of P-gp in hippocampus in SRS rats with drug resistance.