槐定碱致癫痫样作用研究

Epileptic seizure-like effect of Sophora alkaloid sophoridine on experimental animals

目的:观察槐定碱(sophoridine)致痫大鼠清醒核团脑电(IEEG)变化特点;研究痫样特征分类和致痫作用机制。方法:采用慢性埋藏电极记录清醒大鼠核团脑电(intracranial electroencepholography,IEEG)的方法,观察槐定碱对大鼠产生痫样放电的特点,并判断致痫原发部位;采用小鼠模型实施工具药拮抗实验,探讨槐定碱所致癫痫样发作的作用机制及类型。结果:海马齿状回(DG)内颗粒细胞对于槐定碱致痫作用最敏感,其次是内侧穿行通路(PP)和颞叶皮层(TC)。阈下催眠剂量的地西泮、催眠剂量的巴比妥钠可以对抗槐定碱引起的痫样惊厥的发生;对抗最大电休克剂量的苯妥英钠不能对抗槐定碱引起的痫样惊厥的发生,但可以减缓惊厥的发生时间和小鼠的死亡时间。结论:海马内部异常放电在槐定碱致痫作用中可能起到重要作用,海马部位可能是痫样发作的原发部位;槐定碱的致动物癫痫样发作属于临床小发作类型,地西泮是较理想的预防药物。

Objective： To investigate the epileptic seizure-like effect of Sophora alkaloid sophoridine on electroencepholography （EEG） and its possible characteristic and the mechanism of the seizure-like effect. Method： Chronic electron implantation was employed for the intracranial electroencepholography （IEEG） recording in rat, and the traditional anti-seizure drugs were for the mecha- nism study in mice. Result： Compared with the medial pcrforant path （PP） area and the temporal cortex （TC） , the granule cells in hippocampus dentate gyrus （DG）area is more sensitive in the kindling effect by sc sophoridine. Under-threshold hypnotic dosage of di- azepam and the hypnotic dosage of pentobarbital sodium can block the sophoridine kinded seizure in mice, but the phenytoin sodium can not block the seizure, also the dosage of it can block the maximal electroconvulsive shock （MES） seizure. Conclusion： Sophoridine-induced synchronous oscillations in the hippocampus could elicit the generation and development of seizure. And the hippocampus might play the crucial role and be the original part of the seizure. Sophoridine kinded seizure might belong to clonic seizures, and the diazepam is the ideal agent for the treatment.