摘要
The antiepileptic effect of 4-amino-2-methyl-cantharidinimide（AMC） was reported,but its mechanism remains unknown.In this study,we investigated the effects of AMC on a rat model of penicillin-induced epilepsy.The doses of 88 and 22 mg/kg AMC and the dose of 154 mg/kg sodium valproate（VPA） were administered intragastrically（i.g.） 30 min before penicillin injection,respectively.The epileptiform activity was verified by electrocorticographic（ECoG） recordings.The levels of GABA and GABAC receptors in hippocampus were determined by immunohistochemistry,and real-time polymerase chain reaction（RT-PCR） technique was used to detect the mRNA expression of GABAC receptor ρ2.The mean frequency and amplification of spike epileptiform activity were significantly decreased in AMC and VPA-pretreated rats compared with those of non-pretreated penicillin-induced epilepsy（PIE） group.The levels of GABA,GABAC receptors and the mRNA expression of GABAC receptors ρ2 in AMC and VPA-pretreated rats were significantly increased as compared with PIE group.These findings indicate that AMC and VPA have an antiepileptic effect on PIE in rats,and the antiepileptic effect of AMC may be mediated by the GABAC receptors and GABA.
已有胺甲斑蝥素的抗惊厥作用的相关报道,但其作用机制不明,本实验研究了胺甲斑蝥素对GABAC受体的影响。采用青霉素诱发的大鼠癫痫模型,在注射青霉素前30分钟,对应不同分组分别给予灌胃胺甲斑蝥素88mg/kg、22mg/kg,丙戊酸钠154mg/kg。应用脑电图监测大鼠痫样活动时脑电波的变化,免疫组织化学技术测定GABA和GABAC受体在海马区的水平,实时监测的聚合酶链式反应技术测定GABAC受体亚基ρ2的mRNA表达水平。与对照组相比,胺甲斑蝥素组和丙戊酸钠组的痫样活动振幅和频率都明显降低,GABA和GABAC受体在海马区的水平以及GABAC受体亚基ρ2的mRNA表达水平明显增加。实验表明胺甲斑蝥素和丙戊酸钠都可抑制癫痫发作,我们认为氨甲斑蝥素的抗惊厥作用的机制可能是通过调节GABA和GABAC受体水平来实现的。
基金
Scientific and Technological Innovation Foundation of Shanxi Medical University (Grant No. 01200804)
