雌、孕激素在癫痫发病中的作用及其机制研究

The Roles of Estrogen and Progestin in Epileptogenesis and Their Mechanisms of Action

临床资料显示 ,某些女性癫痫患者体内雌、孕激素的周期性变化可能影响癫痫发作的易感性。为了探索雌、孕激素在癫痫发病中的作用 ,阐明其作用机制 ,本工作分别以马桑内酯(CL)侧脑室注射致痫、贝美格 (Be)腹腔注射致痫大鼠为实验对象 ,采用神经电生理、流式细胞免疫荧光、高效液相色谱、免疫细胞化学、原位杂交技术 ,从整体、行为、细胞、分子以及基因水平研究了雌、孕激素对大鼠中枢神经系统 (CNS)功能的影响。研究结果表明 ,卵巢甾体激素属于神经甾体激素 ,其作为新的神经调质对CNS具有广泛的影响 ,它们分别通过调节即刻早期基因、氨基酸类神经递质及神经递质受体而多环节影响CNS的兴奋性。

Clinical data showed that periodic alterations of estrogen and progestin in some women patients with catamenial epilepsy might affect seizure susceptibility. In the present study,in order to explore the roles of estrogen and progestin in epilepsy and elucidate their mechanisms of action, we utilized animal seizure models induced by intracerebroventricular(i.c.v) coriaria lactone(CL) and intraperitoneal(i.p) bemegride(Be), studied the effects of estrogen and progestin on central nervous system(CNS) functions in behavior,electrophysiological,cellular,molecular and gene levels by means of neuroelectrophysiology, flow cytometry, high performance liquid chromatography, immunocytochemical and in situ hybridization techniques. From our observation we concluded that ovarian hormones are neuroactive steroids and new neuromodulaters, they could affect the excitability of CNS by regulating immediate early genes, amino acid neurotransmitters and N methyl D aspartate receptor(NMDAR).