基于生物信息学的急性缺血性脑卒中后心功能不全关键基因筛选及验证  

Screening and validation of key cardiac dysfunction genes after acute ischemic stroke:a bioinformatics analysis

作　　者：孙俊丽 王昭君[2] 韩毅[3,4] SUN Junli;WANG Zhaojun;HAN Yi(College of Anesthesia,Shanxi Medical University,Taiyuan 030002,China;Department of Physiology,School of Basic Medical,Shanxi Medical University,Key Laboratory of Cell Physiology,Ministry of Education,Shanxi Provincial Key Laboratory of Cell Physiology,Taiyuan 030002,China;Depart-ment of Anesthesia,Second Hospital of Shanxi Medical University,Taiyuan 030001,China;Department of Anesthesia,Shuozhou Hospital,Shuozhou 036000,China)

机构地区：[1]山西医科大学麻醉学院,太原030002 [2]山西医科大学基础医学院生理学系,细胞生理学教育部重点实验室,山西省细胞生理学重点实验室,太原030002 [3]山西医科大学第二医院麻醉科,太原030001 [4]朔州市大医院麻醉科,山西朔州036000

出　　处：《中国医科大学学报》2024年第9期769-776,共8页Journal of China Medical University

基　　金：国家自然科学基金青年基金(81400260);山西省应用基础研究基金(20210302123267);山西省卫生健康委科研课题(2022020);首都医科大学重点实验室开放研究课题(DXWL2022-05)。

摘　　要：目的基于生物信息学方法筛选急性缺血性脑卒中(IS)后心功能不全的关键基因及信号通路。方法从基因表达综合(GEO)数据库下载GSE102558数据集,以P<0.05且|log2FC|>0.6筛选差异表达基因(DEG)。Cytoscape软件MCODE插件对蛋白质-蛋白质相互作用(PPI)网络进行功能模块分析,CytoHubba插件筛选核心基因。基因本体(GO)和京都基因和基因组数据库(KEGG)进行富集分析。构建大脑中动脉闭塞模型,实时PCR验证核心基因的表达情况。结果筛选出的DEG中上调385个,下调354个。评分前10位的核心基因分别是Col1a1、Col1a2、Col3a1、Fbn1、Postn、Col5a1、Mmp3、Eln、Acta2、Timp3。GO分析显示主要富集在细胞外基质、胶原纤维组织、血管发育、蛋白酶结合等方面。KEGG分析显示主要在蛋白质消化和吸收、松弛素、AGE-RAGE、血小板活化等通路富集。实时PCR结果显示Col3a1和Postn 2个关键基因在急性IS后心脏组织中表达均下降。结论Co-l3a1和Postn可能与急性IS后心功能不全的发生发展密切相关。Objective To use bioinformatics analysis to identify the key genes and signaling pathways involved in cardiac dysfunction after acute ischemic stroke.Methods The GSE102558 dataset was downloaded from the Gene Expression Omnibus(GEO)database,and genes with values of P<0.05 and|log2FC|>0.6 were identified as being differentially expressed.The MCODE plugin in Cytoscape software performed a functional module analysis of the protein-protein interaction(PPI)network,while the CytoHubba plugin screened for core genes.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were also performed.A middle cerebral artery occlusion model was constructed to verify core gene expression using real-time PCR.Results Among the screened differential genes,385 were upregulated and 354 were downregulated.The top ten core genes were Col1a1,Col1a2,Col3a1,Fbn1,Postn,Col5a1,Mmp3,Eln,Acta2,and Timp3.The GO enrichment mainly involved the extracellular matrix,the collagen fiber tissue,vascular development,and protease binding.KEGG was mainly enriched in protein digestion and absorption,the relaxin pathway,advanced glycation end products-receptor for advanced glycation end products,and platelet activation.Real-time PCR verified that Col3a1 and Postn expressions decreased in the heart tissue after acute ischemic stroke.Conclusion Col3a1 and Postn expressions may be closely associated with cardiac dysfunction occurrence and development after acute ischemic stroke.

关 键 词：急性缺血性脑卒中 心脏 生物信息学 差异表达基因 富集分析 

分 类 号：R743.3[医药卫生—神经病学与精神病学]