冠心病进展相关基因筛选及冠心Ⅱ号方干预靶点的预测  

Identification of Genes Associated with Progression of Coronary Artery Disease and Prediction of Intervention Targets of GuanxinⅡFormula

作　　者：骆金文 刘敏 于燕乔 谭宇 史大卓[1] 马晓娟[1,3] LUO Jinwen;LIU Min;YU Yanqiao;TAN Yu;SHI Dazhuo;MA Xiaojuan(National Clinical Research Center for Chinese Medicine Cardiology,Xiyuan Hospital,China Academy of Chinese Medicial Sciences,Beijing 100091,China)

机构地区：[1]中国中医科学院西苑医院心血管病研究中心,北京100091 [2]北京中医药大学临床医学院西苑医院 [3]中国中医科学院西苑医院中医药保健研究中心,北京100091

出　　处：《中西医结合心脑血管病杂志》2024年第3期393-401,共9页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：国家自然科学基金委员会面上项目(No.82174214,82074418)。

摘　　要：目的:探索冠心病疾病进展相关基因,并预测冠心Ⅱ号方防治冠心病的作用靶点。方法:从基因表达综合数据库(GEO)下载急性心肌梗死(AMI)与稳定型冠心病(SCAD)病人转录组表达谱,通过差异表达分析和加权基因共表达网络分析(WGCNA),筛选冠心病疾病进展相关基因,并针对冠心病进展相关基因进行基因本体(GO)功能分析与京都基因与基因组百科全书(KEGG)通路富集分析。从中药系统药理学数据库与分析平台(TCMSP)数据库下载冠心Ⅱ号方的有效成分及药效靶点,与冠心病疾病进展相关基因进行交集分析,获得冠心Ⅱ号方防治冠心病的潜在靶点。结果:通过差异表达分析比较AMI和SCAD转录组表达谱,共获得166个差异表达基因(DEGs)。通过WGCNA获得与AMI相关的基因模块Black。取DEGs与Black模块的交集,获得64个冠心病疾病进展相关基因。从TCMSP数据库共获得224个冠心Ⅱ号方的药效靶点,将药效靶点与冠心病疾病进展相关基因取交集,得到冠心Ⅱ号方防治冠心病的潜在作用靶点,即过氧化物酶体增殖物激活受体(PPARG)、单核细胞分化抗原CD14(CD14)和细胞色素P4501b1(CYP1B1)。结论:细胞因子信号转导抑制因子3(SOCS3)、嗜酸性粒细胞阳离子相关蛋白(ECRP)、肿瘤坏死因子受体超家族成员10D(TNFRSF10D)、S100钙结蛋白A9(S100A9)等64个基因可能与冠心病疾病进展相关,其中,PPARG、CD14、CYP1B1是冠心Ⅱ号方防治冠心病的潜在作用靶点。Objective:To explore the genes related to the progression of coronary heart disease and predict the target of GuanxinⅡFormula for prevention and treatment of coronary heart disease.Methods:The transcriptome expression profiles of patients with acute myocardial infarction(AMI)and stable coronary heart disease(SCAD)were downloaded from the comprehensive gene expression database(GEO).Differential expression analysis and weighted gene co-expression network analysis(WGCNA)were used to obtain genes related to coronary heart disease progression.Gene ontology(GO)function analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were performed for genes related to coronary heart disease progression.The active components and pharmacodynamic targets of GuanxinⅡFormula were downloaded from the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP)database.The genes related to the progression of coronary heart disease were analyzed,and the potential target of GuanxinⅡFormula for prevention and treatment of coronary heart disease were obtained.Results:A total of 166 differentially expressed genes(DEGs)were obtained by differential expression analysis.The gene module Black related to AMI was obtained by WGCNA.The intersection of DEGs and Black modules was used to obtain 64 genes related to coronary disease progression.A total of 224 therapeutic targets of GuanxinⅡFormula were obtained from TCMSP database.The potential targets of GuanxinⅡFormula for prevention and treatment of coronary heart disease were obtained by intersecting therapeutic targets with genes related to the progression of coronary heart disease,including peroxisome proliferator activating receptor(PPARG),monocyte differentiation antigen CD14(CD14)and cytochrome P4501b1(CYP1B1).Conclusion:Sixty-four genes,including cytokine signal transduction inhibitor 3(SOCS3),eosinophilic cation-associated protein(ECRP),TNFRSF10D and S100A9,might be associated with the progression of coronary heart disease.A

关 键 词：急性心肌梗死 稳定型冠心病 冠心Ⅱ号方 转录组 干预靶点 基因筛选 

分 类 号：R541.4[医药卫生—心血管疾病]