基于铁死亡相关基因构建心肌缺血-再灌注损伤的分子网络及其验证分析  

Construction of Molecular Network for Myocardial Ischemia-Reperfusion Injury Based on Ferroptosis-Related Genes and Its Validation Analysis

作　　者：徐聪聪[1] 叶燕平 黄晓梅 XU Cong-cong;YE Yan-ping;HUANG Xiao-mei(Department of Cardiovascular Medicine,the Second Affiliated Hospital of Nanchang University,Nanchang 330006,China;Department of Gastroenterology,the Second Affiliated Hospital of Nanchang University,Nanchang 330006,China;School of Stomatology,Nanchang Medical College,Nanchang 330052,China)

机构地区：[1]南昌大学第二附属医院心血管内科,南昌330006 [2]南昌大学第二附属医院消化内科,南昌330006 [3]南昌医学院口腔医学院,南昌330052

出　　处：《南昌大学学报（医学版）》2024年第6期42-49,79,共9页Journal of Nanchang University：Medical Sciences

基　　金：江西省卫计委科技计划项目(20185214)。

摘　　要：目的探索心肌缺血-再灌注(I/R)损伤中铁死亡相关基因的表达及功能,通过构建分子网络及其验证分析,为心肌I/R损伤的治疗提供新的分子靶点。方法对GSE108940数据库中的基因表达数据进行标准化处理,利用火山图和热图筛选差异表达基因(DEGs)。结合FerrDb数据库,进行交集分析以识别铁死亡相关的差异表达基因(DEFRGs)。通过聚类分析器R包对这些基因进行GO和KEGG功能富集分析。使用STRING数据库构建蛋白质相互作用(PPI)网络,并利用Friends工具评估关键枢纽基因。通过GSE4105数据集和HL-1小鼠心肌细胞株缺氧-再氧化(OGD/R)模型,验证这些关键基因的表达变化。结果基于GSE108940数据集,通过标准化处理后的基因芯片数据,识别出533个DEGs,包括312个上调和221个下调基因。进一步通过交集分析,与FerrDb数据库中的铁死亡相关基因对比,识别出23个DEFRGs,其中19个上调、4个下调基因。这些基因的功能富集分析涵盖多个关键生物过程,如铁离子运输、细胞内铁离子稳态等,并在多个细胞组成部分和分子功能层面显示其重要性。PPI网络揭示了20个基因节点之间的复杂相互作用,并确定了5个关键枢纽基因:Sqstm1(Sequestosome 1)、转铁蛋白受体(Tfrc)、脂联素2(Lcn2)、细胞周期依赖性激酶抑制剂1A(Cdkn1a)和溶质载体家族40成员1(Slc40a1)。利用GSE4105数据集以及构建的HL-1小鼠心肌细胞株OGD/R模型,均显示这些关键基因在心肌I/R损伤模型中的表达变化。结论本研究基于生物信息学方法构建了心肌I/R损伤相关的铁死亡分子网络,并通过实验初步验证了关键枢纽基因的作用,为未来心肌I/R损伤的治疗提供了潜在的靶点。Objective To explore the expression and function of ferroptosis-related genes in myocardial ischemia-reperfusion(I/R)injury,and to provide new molecular targets for the treatment of myocardial I/R injury by constructing a molecular network and its verification analysis.Methods The gene expression data from the GSE108940 database were standardized,and differentially expressed genes(DEGs)were screened using volcano plots and heatmaps.Intersection analysis was performed with the FerrDb database to identify differentially expressed ferroptosis-related genes(DEFRGs).GO and KEGG functional enrichment analyses were conducted on these genes using the R package of cluster analyzer.The STRING database was employed to construct a protein-protein interaction(PPI)network,and key hub genes were evaluated using the Friends tool.The expression changes of these key genes were validated through the GSE4105 dataset and the hypoxia-reoxygenation(OGD/R)model of HL-1 mouse myocardial cell line.Results Based on the GSE108940 dataset,533 DEGs were identified through the standardized gene chip data,including 312 up-regulated genes and 221 down-regulated genes.Through further intersection analysis and comparison with ferroptosis-related genes in the FerrDb database,23 DEFRGs were identified,including 19 up-regulated and 4 down-regulated genes.The functional enrichment analysis of these genes covered multiple key biological processes,such as iron ion transport and intracellular iron ion homeostasis,and demonstrated their importance in various cellular components and molecular functional levels.The PPI network uncovered complex interactions among 20 gene nodes and identified five key hub genes:Sqstm1(Sequestosome 1),transferrin receptor(Tfrc),lipocalin 2(Lcn2),cyclin-dependent kinase inhibitor 1A(Cdkn1a),and solute carrier family 40 member 1(Slc40a1).Both the GSE4105 dataset and the constructed OGD/R model of HL-1 mouse myocardial cell line demonstrated significant expression changes of these key genes in the myocardial I/R injury model.Con

关 键 词：心肌缺血-再灌注损伤 铁死亡 差异表达基因 功能富集分析 蛋白质相互作用网络 

分 类 号：R34[医药卫生—基础医学]