缺血性心肌病致心力衰竭患者LVAD植入前后关键基因分析  

Analysis of Key Genes in Patients with Heart Failure Caused by Ischemic Cardiomyopathy before and after LVAD Implantation

作　　者：吴旭东 刘宇 王贤良[1] WU Xudong;LIU Yu;WANG Xianliang(Department of Cardiology,First Teaching Hospital of Tianjin University of Traditional Chinese Medicine/National Clinical Research Center For Chinese Medicine Acupuncture and Moxibustion,Tianjin 300381,China)

机构地区：[1]天津中医药大学第一附属医院心血管科国家中医针灸临床医学研究中心,天津300381

出　　处：《医学综述》2023年第6期1208-1213,共6页Medical Recapitulate

基　　金：国家自然科学基金(81904153);国家中医药管理局中医药循证能力建设项目(2019XZZX-XXG007)。

摘　　要：目的基于生物信息学筛选缺血性心肌病(ICM)致心力衰竭(HF)患者在左心室辅助装置(LVAD)植入前后的差异表达基因(DEGs),并分析DEGs的生物学功能及其调控的信号通路。方法从GEO数据库中下载GSE52601基因芯片数据集,共获得24例样本,其中8名正常者,16例ICM致HF患者且进行了LVAD植入。利用GEO2R在线分析软件筛选DEGs,然后对DEGs进行基因本体论(GO)和京都基因与基因组百科全书(KEGG)富集分析。应用STRING数据库构建蛋白质-蛋白质相互作用(PPI)网络,并使用Cytoscape软件(3.9.0)进行可视化展示及核心基因筛选。结果本研究共获得24个DEGs,包含11个上调基因和13个下调基因。GO功能富集分析显示,DEGs在细胞组分层面主要组成肌质、肌质网等细胞成分,在生物学层面主要介导神经元死亡调节,在分子功能层面主要富集于转化生长因子-β结合。KEGG信号通路富集分析显示,DEGs主要调控核因子κB、白细胞介素-17信号通路。PPI网络中筛选出即刻早期基因FOS、早期生长应答因子1(EGR1)、DNA损伤可诱导转录物4(DDIT4)、即刻早期基因FOSB、FK506结合蛋白5五个核心基因。结论LVAD植入后ICM致HF患者心功能改善过程中DEGs主要调控核因子κB、白细胞介素-17信号通路以及EGR1、FOS、DDIT4等核心基因差异表达下调,使得心肌胶原蛋白沉积减少、心肌纤维化的发生发展受到抑制,延缓了心室重构,为进一步探索ICM致HF的治疗机制提供了理论依据。Objective To screen out differentially expressed genes(DEGs)in patients with heart failure caused by ischemic cardiomyopathy before and after implantation of left ventricular assist device(LVAD)based on bioinformatics,and analyze the biological function and regulatory signaling pathway of DEGs.Methods The GSE52601 gene chip dataset was downloaded from the GEO database,and a total of 24 samples were obtained,including 8 normal patients and 16 patients with ICM induced HF who underwent LVAD implantation.GEO2R online analysis software was used to screen DEGs,and then gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were conducted on the DEGs.The protein-protein interaction(PPI)network was constructed using STRING database,and the visualization display and core gene screening were carried out using Cytoscape software(3.9.0).Results A total of 24 DEGs were obtained,including 11 up-regulated genes and 13 down-regulated genes.The GO function enrichment analysis showed that the DEGs mainly participated in the composition of sarcoplasmic and sarcoplasmic reticulum at the cell component level,mainly mediated the regulation of neuronal death at the biological level,and were mainly enriched in transforming growth factor-βcombination at the molecular functional level.KEGG signal pathway enrichment analysis showed that the DEGs mainly regulated nuclear factor-κB,interleukin-17 signaling pathways.Five core genes including immediate early gene FOS,early growth response 1(EGR1),DNA damage inducible transcript 4(DDIT4),immediate early gene FOSB and FK506 binding protein 5 were screened from the PPI network.Conclusion DEGs mainly regulate nuclear factor-κB,interleukin-17 signal pathway,and downregulate the differential expression of core genes such as EGR1,FOS,and DDIT4 during the improvement of cardiac function in patients with heart failure induced by ICM after LVAD implantation,which reduces the deposition of myocardial collagen,inhibits the occurrence and development of myocardial fibrosi

关 键 词：缺血性心肌病 心力衰竭 左心室辅助装置 生物信息学分析 

分 类 号：R541[医药卫生—心血管疾病]