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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 observe the effects of verapamil, a PGP antagonist, on electrophysiological parameters and behavior of PHT and CBZ epileptic rats. Methods A rat model of chronic amygdala igniting epilepsy was established. The drug-resistant group and the treatment-effective group were selected and verapamil was given to observe the effects of after discharge threshold (ADT), post-discharge duration (after discharge duration, ADD) and other electrophysiological indicators and behavior. Results Compared with the drug-resistant control group, ADT [(238.0 ± 32.2) μA] was significantly higher in the drug-resistant group than that in the drug-resistant control group [177.0 ± 23.3] after pretreatment with verapamil μA, P <0.05]. The duration of ADD significantly shortened, and the Racine behavioral grading decreased significantly (P <0.05). Conclusion Verapamil can help AEDs to improve the electrophysiological activity of drug-resistant rats and reduce the grade of post-ignition seizure, suggesting that the effective inhibition of PGP may help to improve the epileptic drug resistance induced by the high expression of multi-drug transporter.