基于线粒体功能障碍探讨急性呼吸窘迫综合征的核心基因OA

Objective:To investigate the roles and mechanisms of mitochondrial dysfunction in acute respiratory distress syndrome(ARDS)using bioinformatics approaches,and to screen for Chinese medicinals with potential therapeutic effects.Methods:ARDS-relat-ed genes and mitochondria-related genes were retrieved from the GEO and MitoCarta3.0 databases respectively.WGCNA was applied to screen key module genes related to ARDS.The intersection of the three gene sets was extracted to obtain potential mitochondrial genes driving the pathogenesis of ARDS.GO and KEGG enrichment analyses for these candidate mitochondrial genes were conducted via the"clusterProfiler"package in R.LASSO and SVM-RFE algorithms were adopted to further screen core genes.The CIBERSORT algorithm was utilized to quantify the relative proportions of immune cell subsets in ARDS samples,and Spearman correlation analysis was per-formed to assess the correlation between core genes and immune cells.Finally,the core genes were imported into the ETCM 2.0 data-base to screen Chinese medicinals with potential therapeutic effects against ARDS.Results:A total of 900 differentially expressed genes(DEGs)were screened in ARDS samples.WGCNA analysis identified 15 key modules correlated with ARDS,among which the MEblue module had the highest correlation with ARDS.The intersection of the 900 ARDS DEGs,1,136 MitoRGs,and 3,150 genes within the MEblue module yielded 45 ARDS-associated mitochondrial genes.GO enrichment analysis revealed that BP were mainly enriched in mi-tochondrial gene expression,mitochondrial translation,mitochondrial transport,and transmembrane protein transport to intracellular or-ganelles;CC were predominantly enriched in the mitochondrial matrix,mitochondrial inner membrane,organellar ribosomes and mito-chondrial ribosomes;MF were primarily enriched in structural constituents of ribosomes,unfolded protein binding,ligase activity,and carbonoxygen lyase activity.KEGG pathway analysis revealed significant enrichment in pathways including pyruvate metabolism,fatty acid biosynthesis,valine,leucine and isoleucine degradation,fatty acid metabolism,and mitophagy.LASSO and SVM-RFE algorithms i-dentified PDK4,TOMM20,MRPS2,ABCB7,and FAM162A as core ARDEGs.Correlation analysis of immune cell infiltration showed that PDK4 was positively correlated with activated dendritic cells and negatively correlated with memory B cells;TOMM20 was positively correlated with plasma cells,CD8+T cells,activated CD4+memory T cells and M2-type macrophages,but negatively correlated with follicular helper T cells and M1-type macrophages;MRPS2 was positively correlated with CD8+T cells and regulatory T cells,and nega-tively correlated with follicular helper T cells,M1-type macrophages and eosinophils;ABCB7 was negatively correlated with activated natural killer cells.Retrieval from the ETCM 2.0 database identified four Chinese medicinals as potential therapeutic candidates regula-ting the five core genes,namely Kuxingren(Armeniacae Semen Amarum),Luobumaye(Apocyni Veneti Folium),Muxiang(Aucklandiae Radix)and Gouqizi(Lycii Fructus).Conclusion:ARDS progression is associated with mitochondrial dysfunction,which may drive its initiation and progression by regulating immune cell functions.