黄连治疗癫痫的协同作用及对P-糖蛋白介导的抗癫痫药脑转运的调节作用

Study of Coptidis Rhizoma on the Synergism to Epilepsy and the Regulation to Brain Delivery of Antiepileptic Drugs Mediated by P-glycoprotein

目的考察黄连协同抗癫痫药治疗癫痫的疗效及黄连对P-糖蛋白介导的抗癫痫药透过血脑屏障的影响,评价黄连对癫痫的防治作用。方法选用P-糖蛋白抑制剂维拉帕米和常用抗癫痫药卡马西平,使用戊四唑和士的宁制备小鼠癫痫模型,观察并对比卡马西平单用与联用低、中、高剂量黄连的小鼠潜伏期、惊厥率和死亡率的差异。小鼠分组并灌胃卡马西平、卡马西平加黄连及卡马西平加维拉帕米后,测定脑组织卡马西平浓度并比较。结果黄连可显著增强卡马西平对抗戊四唑、士的宁所引起的癫痫作用,延长潜伏期和降低惊厥率(P<0.05),明显提高卡马西平的脑浓度(P<0.05)。结论黄连对癫痫的治疗有良好的增效作用。

OBJECTIVE To investigate the efficacy of Coptidis Rhizoma combined with antiepileptic drugs on epilepsy and the effect of Coptidis Rhizoma on the passing of antiepileptic drugs through blood-brain barrier mediated by P-glycoprotein, thus evaluate the preventive and therapeutic effect of Coptidis Rhizoma on epilepsy. METHODS Verapamil as a P-glycoprotein inhibitor and carbamazepine as a common antiepileptic drug were selected. The mice epilepsy models were prepared by pentylenetetrazole and strychnine, respectively. The seizure latency, convulsion rate and mortality of the mice intragastrically administrated carbamazepine alone or with low, middle and high dose of Rhizoma Coptidis were observed and contrasted. Mice were divided into groups and orally administrated carbamazepine, carbamazepine with Coptidis Rhizoma and carbamazepine with verapamil, and then the brain concentration of carbamazepine was determined and compared. RESULTS Coptidis Rhizoma significantly enhanced the antagonism of carbamazepine to pentylenetetrazole and strychnine, which prolonged the seizure latency and reduced the convulsion rate（P〈0.05）. The brain concentration of carbamazepine was also markedly raised by Coptidis Rhizoma（P〈0.05）. CONCLUSION Coptidis Rhizoma has good synergetic effect on the treatment of epilepsy.