氯化锂-匹罗卡品诱导癫痫大鼠海马组织差异表达circRNA的筛选及功能分析  

Screening and Functional Analysis of Differentially Expressed CircRNA in Hippocampus of Rats with Epilepsy Induced by Lithium Chloride-Pilocarpine

作　　者：黄亚辉 杨萍 朱勇 王琴 卢军 贺冰[2] 张熙 HUANG Ya-hui;YANG Ping;ZHU Yong;WANG Qin;LU Jun;HE Bing;ZHANG Xi(Epilepsy Treatment Center,Brain Hospital of Hunan Province(Clinical Medical College,Hunan University of Chinese Medicine),Changsha 410007,China;The Second Affiliated Hospital of Hunan University of Chinese Medicine,Changsha 410007,China)

机构地区：[1]湖南省脑科医院(湖南中医药大学临床医学院)癫痫中心,长沙410007 [2]湖南中医药大学附属第二医院中医科,长沙410007

出　　处：《神经损伤与功能重建》2022年第6期315-319,共5页Neural Injury and Functional Reconstruction

基　　金：国家自然科学基金(No.81874429);湖南省卫生计生委科研课题(No.20200009,B2019047);湖南省自然基金(No.2019JJ80027,2020JJ5294);湖南省中医药管理局重点项目(No.202145);湖南省教育厅科研项目(No.19B440)。

摘　　要：目的:探究氯化锂-匹罗卡品诱导癫痫大鼠海马组织差异表达共价闭合、单链环状RNA(circRNA)及功能分析。方法:通过构建氯化锂-匹罗卡品癫痫大鼠模型,取癫痫大鼠及对照大鼠海马组织通过Illumina高通量测序平台进行转录组测序,并通过EdgeR包对circRNA进行差异分析、通过R语言进行GO及KEGG信号通路富集分析,通过Targetscan与miRanda软件进行circRNA与miRNA互作分析寻找circRNA核心调控靶标。结果:对照组及癫痫组大鼠海马的circRNA进行差异分析获得的262个差异表达circRNA,信号通路富集分析发现与胞蛋白修饰过程、蛋白质变性过程、树突形态调控、神经元分化调节、离子跨膜转运的调节等生物过程相关。并进一步确定了可能与circRNA存在互作的核心调控miRNA,包括miR-322-5p、miR-322-3p、miR-323-5p、miR-323-3p、miR-301a-5p、miR-301a-3p、miR-324-5p、miR-324-3p等。结论:本研究筛选了氯化锂-匹罗卡品点燃癫痫大鼠与正常大鼠脑组织差异circRNA,系统地分析了其可能的作用功能机制,为癫痫诊断或治疗寻找到可靠的生物标志物。Objective:To investigate the differential expression of circRNA and its function in hippocampal tissues of epileptic rats induced by lithium chloride-pilocarpine.Methods:The epileptic rat model was established using lithium chloride-pilocarpine.Hippocampal tissue of epileptic rats and control rats was collected for transcriptome sequencing by the Illumina high-throughput sequencing platform.The differences in circRNA were analyzed with the edgeR package.GO and KEGG pathway enrichment analysis was performed in R.Targetscan and miRanda were used for circRNA-miRNA interaction software analysis to find circRNA core control targets.Results:We obtained 262 differentially expressed circRNAs by differential analysis of hippocampal circRNA in the control group and epilepsy group.Signal pathway enrichment analysis revealed that these circRNAs were associated with the cytoprotein modification process,protein degeneration process,dendritic morphology regulation,neuron differentiation regulation,ion transmembrane transport,and other biological processes.We further identified core regulatory miRNAs that may interact with circRNA,including miR-322-5p,miR-322-3p,miR-323-5p,miR-323-3p,miR-301a-5p,miR-301a-3p,miR-324-5p,miR-324-3p,etc.Conclusion:In this study,the difference in brain tissue circRNA between lithium chloride-pilocarpine epileptic rats and normal rats was screened and the possible mechanism of function was systematically analyzed so as to find a reliable biomarker for the diagnosis and treatment of epilepsy.

关 键 词：氯化锂-匹罗卡品 癫痫 circRNA MIRNA 

分 类 号：R741[医药卫生—神经病学与精神病学] R741.02[医药卫生—临床医学] R742.1