Objectives: To explore the mRNA differential expressions and the sequential change pattern in acute myocardial infarction (AMI) mice.
Methods: The AMI mice relevant dataset GSE4648 was downloaded from Gene Expression Omnibus (GEO). In the dataset, 6 left ventricular myocardial tissue samples were selected at 0.25, 1, 4, 12, 24 and 48 h after operation in AMI group and sham control group, and 6 left ventricular myocardial tissue samples were selected in blank control group, a total of 78 samples were analyzed. Differentially expressed genes (DEGs) were analyzed by R/Bioconductor package limma, functional pathway enrichment analysis was performed by clusterProfiler, protein-protein interaction (PPI) network was constructed by STRING database and Cytoscape software, the key genes were identified by Degree topological algorithm, cluster sequential changes on DEGs were analyzed by Mfuzz.
Results: A total of 1 320 DEGs were associated with the development of AMI. Functional enrichment results included cellular catabolic process, regulation of inflammatory response, development of muscle system and vasculature system, cell adhesion and signaling pathways mainly enriched in mitogen-activated protein kinase (MAPK) signaling pathway. The key genes of AMI included MYL7, TSC22D2, HSPA1A, BTG2, NR4A1, RYR2 were up-regulated or down-regulated at 0.25-48 h after the occurrence of AMI.
Conclusions: The functional signaling pathway of DEGs and the sequential expression of key genes in AMI may provide a reference for the forensic identification of AMI.
目的: 探寻急性心肌梗死（acute myocardial infarction，AMI）小鼠心肌组织mRNA的差异表达及时序性变化规律。方法: 从基因表达综合数据库中下载小鼠AMI相关数据集GSE4648，筛选数据集中AMI实验组和假手术对照组术后0.25、1、4、12、24、48 h 6个时间点左心室心肌组织样本各6个，空白对照组左心室心肌组织样本数据6个，共78个样本数据进行分析。使用R软件包中的Bioconductor package limma分析差异表达基因，使用clusterProfiler进行功能通路富集分析，使用STRING数据库及Cytoscape软件构建蛋白质-蛋白质相互作用关系（protein-protein interaction，PPI）网络、Degree拓扑算法确定关键基因，最后使用Mfuzz进行时序性聚类分析。结果: 共1 320个差异表达基因与AMI发生发展有关。功能富集结果包括细胞分解代谢过程、炎症反应的调控、肌肉系统及脉管系统发育、细胞黏附等，信号通路主要富集于丝裂原活化蛋白激酶信号通路。AMI关键基因包括MYL7、TSC22D2、HSPA1A、BTG2、NR4A1、RYR2，在AMI发生后0.25~48 h出现不同程度的上调或下调。结论: AMI中差异表达基因的功能信号通路及关键基因的时序性表达可能为AMI的法医学鉴定提供参考。.
Keywords: acute myocardial infarction; bioinformatics; differentially expressed genes; forensic pathology; mice; sequential expression.