维拉帕米对耐苯妥英钠和卡马西平癫癎模型大鼠电生理和行为的影响

Effect of verapamil on electrobiological activity and seizure behavior in phenytoin-carbamazepine resistant rats

目的观察 P-糖蛋白(PGP)拮抗剂维拉帕米对耐苯妥英钠(PHT)和卡马西平(CBZ)癫癎大鼠电生理指标和行为学的影响。方法建立慢性杏仁核点燃癫癎大鼠模型,筛选出耐药组和治疗有效组,给予维拉帕米,观察其对各组大鼠后放电阈值(after discharge threshold,ADT)、后放电时程(after discharge duration,ADD)等电生理指标和行为学的影响。结果相对于耐药对照组,耐药组大鼠在预先给予维拉帕米后,使用抗癫癎药物后 ADT[(238.0±32.2)μA]明显高于耐药对照组[(177.0±23.3)μA,P<0.05];ADD 时程明显缩短,Racine 行为分级明显下降(P<0.05)。结论维拉帕米可以协助抗癫癎药物(AEDs)改善耐药大鼠的电生理活动,降低点燃后发作分级,提示有效抑制 PGP 有助于改善多药转运体高表达导致的癫癎耐药。

Objective To invesgate the effect of P-glycoprotein （PGP） inhibitor, verapamil, on electrobiological activity and seizure behavior in phenytoin-carbamazepine （PHT-CBZ） resistant rats. Methods The model of medically intractable epilepsy was established by kindling of amygdale. Verapamil was applied to PHT-CBZ resistant rats, followed by the observation on after discharge threshold （ADT）, after discharge duration （ADD） and seizure activity. Results Compared with the control group, the ADT was higher in PHT-CBZ resistant rats peritoneally injected with verapamil （ （238.0 ±32. 2） uA vs （ 177. 0 ± 23.3 ） uA, P 〈 0. 05 ） ; verapamil shortened the ADD, reduced the Racine＇ s behavior degree （P 〈0. 05）. Conclusions Specific inhibitors of PGP could improve the electrobiological activity and seizure behavior in PHT-CBZ resistant rats. It is benefit to inhibit PGP for multidrug resistant medically intractable epilepsy.