心肌梗死后心力衰竭大鼠外周血细胞基因组学特征

Genomic Characteristics of Peripheral Blood Cells in Rats with Heart Failure After Myocardial Infarction

目的采用生物信息学工具分析心肌梗死(MI)后心力衰竭(HF)大鼠外周血单个核细胞基因组学特征。方法在GEO公共数据库中选取假手术组(Sham组)和左冠状动脉结扎诱导MI后的HF组大鼠基因芯片,通过GEO2R在线分析工具筛选两组差异基因,并对差异基因进行GO功能富集分析、KEGGPathway富集分析及蛋白相互作用分析。结果基因芯片共有29214个基因,其中表达上调(logFC>0)的基因259个,表达下调(logFC<0)的基因216个,差异有统计学意义(P<0.05)。在其中筛选出表达上调、下调最显著的基因各50个(共计100个基因)进一步分析。GO功能富集分析结果显示,100个差异基因主要在细胞膜、细胞内膜系统、细胞核、细胞外空间等成分中,具有调控蛋白质结合、转运蛋白活性等分子功能,涉及细胞应激、免疫、通信、代谢、凋亡等生物过程。KEGG Pathway富集分析结果显示,100个差异基因主要参与了免疫信号通路、细胞自噬等细胞信号转导过程。STRING分析结果显示,免疫过程相关分子(KLRC1、KLRC2、KLRD1等)、趋化因子家族(CCR6、CXCR6等)、调节细胞周期、遗传物质修复(PTTG1、CDKN3,TOP2A等)多个分子在相互作用网络中处于关键节点。Cytoscape的MCODE分析显示,KLRC1、KLRC2、KLRD1等与免疫过程相关的分子在大鼠MI后HF的发展过程中发挥了核心作用。结论MI后HF的发生发展是一个综合性过程,细胞应激、免疫、通信、代谢、凋亡等生物过程,细胞免疫信号通路,细胞自噬的启动参与其中,而免疫过程处于核心地位,这可能为今后寻找药物治疗新靶点提供参考。

Objective To analyze the genomic characteristics of peripheral blood mononuclear cells in heart failure(HF)rats after myocardial infarction(MI)with bioinformatics tools.Methods The sham operation group(Sham group)and the HF group rats after MI induced by left coronary artery ligation were selected from the GEO public database.The difference genes between the two groups were screened by the GEO2R online analysis tool,and the differences were analyzed.The genes are subjected to GO function enrichment analysis,KEGG Pathway enrichment analysis and protein interaction analysis.Results There were 29214 genes in the gene chip,of which 259 genes were up-regulated(logFC>0)and 216 genes were down-regulated(logFC<0)(P<0.05).Among them,50 genes with the most significant up-regulation and down-regulation(100 genes in total)were screened for further analysis.The results of GO functional enrichment analysis showed that the 100 differential genes were mainly located in the cell membrane,cell inner membrane system,cell nucleus and extracellular space and other components,with molecular functions such as regulating protein binding and transporter activity,involving biological processes such as cell stress,immunity,communication,metabolism and apoptosis.The results of KEGG Pathway enrichment analysis showed that 100 differential genes were mainly involved in immune signal pathways,autophagy and other cell signal transduction processes.STRING analysis results showed that immune process related molecules(KLRC1,KLRC2,KLRD1,etc.),chemokine family(CCR6,CXCR6,etc.),cell cycle regulation,genetic material repair(PTTG1,CDKN3,TOP2A,etc.)multiple molecules were at key nodes in the interaction network.Cytoscape's MCODE analysis showed that molecules related to immune processes such as KLRCI,KLRC2,KLRDI and other molecules played a central role in the development of HF after MI in rats.Conclusion The occurence and development of HF after MI is a comprehensive process in which biological processes such as cellular stress,immunity,communication,metabolism,apoptosis,cellular immune signaling pathways,and cellular autophagy are involved,and the immune process is at the core.This may provide a reference for finding new targets for drug therapy in the future.