新的热性惊厥免疫相关基因的筛选及功能研究

热性惊厥（Febrile Seizures,FS）是一种主要发生在婴幼儿和儿童时期中枢神经系统功能异常综合征，流行病学调查显示这类儿童发生癫痫的危险是一般儿童的10倍，严重影响广大患儿的智力发育和身心健康。目前FS确切发病机制尚不清楚，最新研究表明免疫炎症反应在FS的发生发展中起到重要作用，如何发现新的免疫相关基因并探讨其致病机制是防治FS的关键。我们前期工作中通过人工定向选择和交配繁育的方法，筛选出热性惊厥敏感模型鼠和耐受模型鼠，并利用表达谱基因芯片寻找到44个可能的热性惊厥免疫相关易感新基因。本项目将进一步利用表达谱基因芯片和DNA甲基化芯片在模型鼠后代上确证热性惊厥免疫相关易感新基因，从分子、细胞、动物水平深入探讨免疫相关易感基因介导的热性惊厥发病机制，丰富和完善热性惊厥的神经免疫和表观遗传调控假说，为防治此类疾病提供理论和实验依据。

Febrile Seizures (FS) are the most common type of specific epilepsy syndrome in infants and young children. Epidemiological studies have reported these children have 10 fold increases in risk for subsequent epilepsy, associated with mental retardation and physical development disorder. Increasing evidence supports the involvement of immune and inflammatory processes in the etiopathogenesis of seizures. 10 susceptibility gene loci have been found by genetic linkage analysis of numerous FS family, including immune-related genes such as IL1β, IL6 and IL10. How to find additional immune inflammation-related genes and pathogenic mechanism is the key for treatment and prevention of FS. Our previous work has established a stable method to sort out two rat phenotypes: FS-sensitive and FS-tolerance based on assortative mating and directional or stabilizing selection. 44 new susceptibility immune inflammation-related genes of FS were found from gene expression profile. The present project will further investigate how the immune inflammation-related genes is involved in the onset of FS, on the basis of molecular, cellular and whole-animal experiments. Future work will be expected to establish prediction model of FS clinically thus to fulfill and enrich the hypothesis of neuro-immunity and epigenetic regulation in the febrile seizure onset.