热性惊厥敏感鼠与耐受鼠的建立及海马差异表达基因的筛选研究  

Construction of febrile seizures sensitive, tolerance rats and screening of differential expression genes of febrile seizures hippocampus

作　　者：韦睿[1] 张玮[1] 于恩彦[2] 

机构地区：[1]昆明医科大学第一附属医院急诊科,云南昆明650031 [2]浙江省人民医院精神科,浙江杭州310014

出　　处：《中国生化药物杂志》2015年第2期74-79,共6页Chinese Journal of Biochemical Pharmaceutics

基　　金：2011年省医药卫生计划（2011KYA012）

摘　　要：目的 建立热性惊厥（febrile seizures,FS）大鼠模型,筛选易感基因并探讨其相关的机制.方法 选取50只SPF级雄性SD大鼠21日龄,通过发病率分析筛选热性惊厥敏感鼠与耐受鼠;通过FS敏感组和耐受组差异（gene ontology,GO）功能分析,差异Pathway分析,差异表达基因间相互作用关系网络分析,差异表达基因共表达网络分析,实时定量PCR验证基因芯片数据方法研究其机制.结果 筛选获得FS敏感鼠和FS耐受鼠2种不同表型的FS模型鼠;热水浴诱导惊厥和KA诱导癫痫实验结果表明FS敏感鼠比耐受鼠表现出更强的惊厥发作现象;2种不同表型的FS模型鼠的表达谱芯片数据分析获得了1140个差异表达基因,其中包括602个上调基因,538个下调基因,并获得了差异显著的GO功能分类;差异表达基因间相互作用网络分析与白介素-6（interlukin-b,IL-6）IL-6有着紧密的联系;差异表达基因共表达网络分析得到共有174个共表达能力发生巨大变化的基因.同时,实时定量PCR验证结果与基因芯片表达一致,表明基因芯片数据的可靠性.结论 2种不同表型FS模型鼠的建立提示表观遗传机制可能参与FS疾病的发生发展;大鼠海马全基因组表达谱芯片分析结果提示免疫炎症、离子通道、代谢等多种因素可能在FS发生发展中起重要作用.] Objective To establish the animal model of febrile seizures（ FS）, screen susceptibility genes and investigate the related pathogenesis. Methods 50 SPF male SD rats （aged 21 days） were selected,screened febrile seizure sensitive and tolerant rats by the incidence of FS. Differences in gene ontology （GO） function, pathway, network interaction of genes differential expression, and differential expression of gcne co-expression network were analyzed between FS sensitive group and tolerant group. The validation of gene chip data method was analyzed by Real-time PCR. Results Access to two different phenotypes of FS rat model of screening, including FS sensitive rats and FS tolerance rats. After 43 hot water bath treatment, the incidence of FS sensitive rats rate with increasing passage number and gradually increase. Hot water bath induced seizures and KA induced epilepsy experimental results showed that the FS sensitive rats exhibited stronger seizure phenomenon than tolerance rats. Obtained 1140 differentially expressed genes by expression of two different phenotypes of FS rat models in microarray data analysis, including 602 up-regulated and 538 down regulated genes, and obtained the GO functional classification differences. Differentially expressed genes interaction network analysis showed that were closely with IL-6, The co-expression network analysis,there were 174 gene of co-expression ability changed tremendous. At the same time, real time quantitative PCR validation results consistent with gene chip expression, showed that the reliability of microarray data. Conclusion Rat model of FS suggested that epigenetic regulation may play an important role in the pathogenesis of FS. Meanwhile, rat hippocampal gene microarray results suggest that many factors （ immunity,ion channels, metabolism et. al） may paly a vital role in the pathogenesis of FS.

关 键 词：热性惊厥 基因芯片 差异表达基因 

分 类 号：R363[医药卫生—病理学]