作者：杨翠1 ，郑思道 2 ，陈少军 1

单位：

1.101400 北京市怀柔区中医医院心内科；2.100039 北京市中西医结合医院心内科；通信作者：郑思道，E-mail：zhengsidao@sina.com

Units：

1.Department of Cardiology，Huairou Hospital of Traditional Chinese Medicine，Beijing 101400，China；2.Department of Cardiology，Beijing Hospital of Integrated Traditional Chinese and Western Medicine，Beijing 100039，China；Corresponding author：ZHENG Sidao，E-mail：zhengsidao@sina.com

关键词：

心力衰竭；心肌梗死；生物信息学；基因；大鼠；心肌；分子功能；信号传导

Keywords：

Heart failure；Myocardial infarction；Bioinformatics；Genes；Rats；Myocardium；Molecularfunction；Signal transduction

CLC：

R 541.6　R 542.22

DOI：

DOI：10.3969/j.issn.1008-5971.2020.01.005

Funds：

北京市优秀人才培养资助青年骨干个人项目（2014000057592G296）

摘要：

背景　药物是心力衰竭（HF）治疗的基石，而基因组学技术正逐渐成为 HF 新药研发的关键领域之一。目的　采用生物信息学工具分析心肌梗死后 HF 大鼠左心室心肌基因组学特征。方法　在 GEO 数据库中选取假手术组（Sham 组）和冠状动脉结扎诱导的心肌梗死后 HF 组（HF 组）大鼠基因芯片，通过 GEO2R 在线软件筛选两组差异基因并对差异基因进行 GO 功能富集分析、KEGG Pathway 富集分析及蛋白相互作用分析。结果　（1）筛选出表达上调、下调最显著的基因各 20 个。（2）GO 功能富集分析结果显示，40 个差异基因富集在细胞膜、内膜系统及细胞外空间等细胞成分中，可参与调控蛋白质结合、离子结合、转运活性等分子功能，涉及应激、多细胞生物过程、生理调节等多个生物学过程。 （3）KEGG Pathway富集分析结果显示，40个差异基因主要参与心肌细胞中的肾上腺素能信号传导。 （4）STRING 分析结果显示，纤维粘连蛋白 1、骨膜蛋白、结缔组织生长因子、分泌型磷蛋白 1、成纤维细胞生长因子 7、分泌型卷曲相关蛋白 2 等多个蛋白在相互作用网络中处于关键节点。结论　应激、多细胞生物过程、生理调节等多个生物学过程及心肌细胞肾上腺素能信号传导通路参与心肌梗死后 HF 的发生发展。

Abstract：

Background　Drug is a cornerstone of anti-heart failure（HF）therapy，and genomic technology isgradually becoming one of key areas in the new drug development for HF. Objective　To analyze the genomic characteristics ofleft ventricular myocardium in rats with HF caused by myocardial infarction by using bioinformatic tools. Methods　Gene chips insham group（rats received sham operation）and HF group（rats with HF caused by coronary artery ligation-induced myocardialinfarction）were selected in GEO database，and then GEO2R online software was used to identify the differentially expressedgenes，moreover differentially expressed genes were analyzed by GO functional enrichment analysis，KEGG Pathway enrichmentanalysis and protein interaction analysis. Results　（1）Twenty up-regulated genes expressed most significantly were screenedas well as 20 down- regulated genes.（2）GO functional enrichment analysis results showed that，the 40 differentially expressedgenes were enriched in components of cells，such as cell membranes，intimal systems and extracellular space，and they couldregulate the protein binding，ion binding，transport activity and other molecular functions involving stress，multicellularbiological processes，physiological regulation and other biological processes.（3）KEGG Pathway enrichment analysis resultsshowed that，the 40 differentially expressed genes were mainly involved in the adrenergic signaling pathways in myocardialcells.（4）STRING analysis results showed that，fibronectin 1，periosteal protein，connective tissue growth factor，secretedphosphoprotein 1，fibroblast growth factor 7 and secreted frizzled related protein 2 were at key nodes in the interaction network.Conclusion　Stress，multicellular biological processes，physiological regulation and other biological processes and adrenergicsignaling pathways in myocardial cells may be involved in the occurrence and development of HF caused by myocardial infarctionin rats.

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