基于生物信息学分析的呼吸机相关肺损伤免疫因子及信号通路预测  

Prediction of immune factors and signal pathways in ventilator-associated lung injury based on bioinformatics analysis

作　　者：刘欢 曹袁媛[1] 张雷[1] 刘学胜[1] 顾尔伟[1] LIU Huan;CAO Yuanyuan;ZHANG Lei;LIU Xuesheng;GU Erwei(Department of Anesthesiology,The First Affiliated Hospital of Anhui Medical University,Hefei,Anhui 230022,China)

机构地区：[1]安徽医科大学第一附属医院麻醉科,安徽合肥230022

出　　处：《安徽医药》2022年第1期49-53,I0001,共6页Anhui Medical and Pharmaceutical Journal

基　　金：安徽医科大学第一附属医院院内青年培育计划项目(2019kj14)。

摘　　要：目的探讨呼吸机相关肺损伤(ventilator-induced lung injury,VILI)发生过程中基因表达和生物学过程的改变,为VILI的分子机制研究提供生物信息学依据。方法在公共基因表达数据库(gene expression omnibus)检索2019年12月前与VILI相关的基因表达谱数据,下载GSE86229基因表达谱数据,并选择其中两组数据(对照组和高潮气量机械通气组)进行后续分析。首先通过标准化和注释对基因表达谱进行预处理,然后选用Limma方法筛选差异表达基因(differentially expressed genes,DEGs)。随后对筛选出的DEGs进行聚类分析,以及基因本体论(gene ontology,GO)和信号通路(KEGG)富集分析。最后,通过STRING数据库、Cytoscape分析蛋白质相互作用网络中关键蛋白质。结果数据预处理后初步获取了20310个基因,并筛选出337个DEGs。富集分析结果显示DEGs主要参与细胞对炎症、脂多糖和中性粒细胞趋化的生物过程,并主要富集于TNF信号通路;蛋白质相互作用网络分析发现白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、整联蛋白αM(ITGAM)、白细胞介素1β(IL-1β)和Toll样受体2(TLR-2)为关键蛋白质。结论生物信息学分析结果显示VILI与炎症反应过程密切相关,可能与IL-6、TNF-α、ITGAM、IL-1β和TLR-2免疫因子密切相关,TNF信号通路在VILI发生过程中起到重要的作用。Objective To explore the changes of gene expression and biological process during the occurrence of ventilator-induced lung injury(VILI),and to provide a bioinformatics basis for the study of the molecular mechanism of VILI.Methods VILI-related gene expression profile data from the Gene Expression Omnibus before December 2019 were retrieved,the GSE86229 gene expression microarray were downloaded,and two of the data(control group and high tidal volume mechanical ventilation group)for follow-up analysis were selected.Firstly,the gene expression microarray was pretreated by standardization and annotation,and then the differentially expressed genes(DEGs)were screened by the limma method.Then the selected DEGs were analyzed by cluster analysis,Gene Ontology(GO),and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.Finally,the key proteins in the protein-protein interaction network were analyzed by the STRING database and Cytoscape.Results After data preprocessing,20310 genes were obtained and 337 DEGs were screened out.The results of enrichment analysis showed that DEGs were mainly involved in the biological process of cell chemotaxis to inflammation,lipopolysaccharide,and neutrophils,and were mainly enriched in TNF signaling pathway.Protein-protein interaction network analysis showed that interleukin-6(IL-6),Tumor necrosis factorα(TNF-α),IntegrinαM(ITGAM),Interleukin 1β(IL-1β),and Toll-like receptor 2(TLR-2)were key proteins.Conclusion Results of bioinformatics analysis show that VILI is closely related to the inflammatory process,and maybe closely related to IL-6,TNF-α,ITGAM,IL-1β,and TLR-2 immune factors.TNF signal pathway plays an important role in the development of VILI.

关 键 词：呼吸机相关性肺损伤 计算生物学 生物信息学分析 白细胞介素-6 肿瘤坏死因子-α 

分 类 号：R563[医药卫生—呼吸系统] Q811.4[医药卫生—内科学]