临床抗癫痫新药治疗的动物实验

Animal Experiments on Clinical Novel Anti-epileptic Drugs in Therapy of Epilepsy

目的:对比临床较常用的几种抗癫痫新药与传统抗癫痫药苯妥英钠长期单药治疗慢性颞叶癫痫大鼠的疗效与安全性。方法:用海仁酸制成慢性颞叶癫痫的大鼠模型,临床常用维持剂量的苯妥因钠、奥卡西平、拉莫三嗪、妥泰根据成人剂量换算为大鼠剂量分别为37．50mg/Kg、125mg/Kg、28．13mg/Kg、15．63mg/Kg。每日灌胃,连续90天后,观察并比较各用药组大鼠脑电功率谱,学习记忆能力,血液常规,肝功能的变化情况。结果:90天后,与造模组相比,苯妥因钠、奥卡西平、拉莫三嗪、妥泰各组脑电活动均改善,其中以拉莫三嗪组最明显。水迷宫测试中:奥卡西平组较好;各用药组对造血、肝功能的影响与造模组及正常对照组相比无统计学意义。结论:对于慢性颞叶癫痫大鼠,拉莫三嗪改善脑电最明显,奥卡西平明显改善认知功能,疗效优于妥泰和苯妥英钠。

Objective：To investigate the efficacy and safety of several novel anti-epileptic drugs （AEDs）, more commonly used in clinical practice, including Phenytoin, Oxcarbazepine,Lamotrigine and Topiramate,which were used to treat chronic temporal lobe epileptic （TLE） rats in long-term and monotherapy compared with phenytoin□a kind of traditional antiepileptic drug. Methods：The rat model of temporal lobe epilepsy was produced by using kainic acid. Maintenance dose of phenytoin sodium, oxcarbazepine, lamotrigine, topiramate were given to the rats, according to the weight of adult converted into rats＇ dose： 37.50mg/Kg, 125mg/Kg, 28.13mg/Kg, 15.63mg/Kg,daily gavage for 90 consecutive days.the rats were observed the changes of power spectra of EEG, learning and memory capacity ,blood forming and liver function. These results were analysed finally. Results：After 90 days,compared with model group,power spectra performance in each group with drugs was improved, specially in lamotrigine group.In the examining of Morris water maze,oxcarbazepine group achieved better results, and there were no statistical significance in blood forming or liver fimction among each group with medicine compared with model and normal groups. Conclusion：Lamotrigine has the best efficacy in improving power spectra activity for the rats with chronic temporal lobe epileptic. Oxcarbazepine can improve rats＇cognitive ability and its therapeutic effect is superior to topiramate and phenytoin TLE rats.