慢性阻塞性肺疾病差异基因与中药预测的生物信息学分析

吴思骐 刘建博

摘要 目的：通過生物信息学技术分析比较慢性阻塞性肺疾病（COPD）患者与健康人的基因芯片数据，初步筛选COPD的差异表达基因，并借助差异表达基因预测治疗COPD的潜在中药药物。方法：首先通过R分析GSE27597和GSE106986基因数据，得到139个差异表达基因，对差异表达基因进行基因本体（GO）富集分析，并通过String数据库、Cytoscape软件及其插件分析得到14个核心基因，然后对核心基因进行Reactome、KEGG、PANTHER等通路注释，最后通过核心基因与医学本体信息检索平台（Coremine Medical）相互映射，筛选治疗COPD的中药。结果：通过MCODE筛选出14个核心基因包括MMP8、PTX3、DEFA4、CHRM2、FPR2、CX3CR1、FPR1、ORM1、APLNR、PPBP、CHIT1、AGTR2、ARG1，与中性粒细胞脱颗粒、先天免疫系统、趋化因子信号通路等密切相关，其中FPR1和CX3CR1通过影响中性粒细胞向肺部的迁移活动成为COPD病理变化的关键。治疗COPD的潜在中药药物包括黄连、黄芪、黄芩、半夏、丹参、厚朴、姜黄、郁金、瓜蒌等。结论：部分基因会促进香烟烟雾暴露诱发COPD的发生，通过miRNA进行调节可能是中药治疗COPD的潜在作用机制。

关键词 差异表达基因;慢性阻塞性肺疾病;微小RNA;中药;香烟烟雾

Abstract Objective：By analyzing and comparing the gene chip data of chronic obstructive pulmonary disease （COPD） patients and healthy people through bioinformatics technology，the differentially expressed genes of COPD are initially screened，and the potential Chinese medicinal drugs for the treatment of COPD are predicted with the help of differentially expressed genes.Methods：The gene expression profiles of lung tissues of COPD cases and healthy cases were obtained from GSE27597 and GSE106986 of the Gene Expression Omnibus.A otal of 139 differentially expressed genes were obtained，and we performed gene ontology （GO） enrichment analysis of differentially expressed genes，and obtained 14 core genes through String database，Cytoscape software and its plug-in analysis，and then we performed Reactome，KEGG，PANTHER and other pathways on the core genes.Finally through the mutual mapping between core genes and the medical ontology information retrieval platform （Coremine Medical），we screened Chinese medicinal for the treatment of COPD.Results：A total of 14 core genes screened by MCODE including MMP8，PTX3，DEFA4，CHRM2，FPR2，CX3CR1，FPR1，ORM1，APLNR，PPBP，CHIT1，AGTR2，ARG1，and neutrophil degranulation，innate immune system，chemokines signal pathways were closely related，among which FPR1 and CX3CR1 have become the key to the pathological changes of COPD by affecting the migration of neutrophils to the lungs.Potential Chinese medicinals for the treatment of COPD include Rhizoma Coptidis，Radix Astragali seu Hedysari，Radix Scutellariae，Rhizoma Pinelliae，Radix Salviae Miltiorrhizae，Cortex Magnoliae Officinalis，Rhizoma Curcumae Longae，Radix Curcumae，Fructus Trichosanthis.Conclusion：Some genes can promote the occurrence of COPD induced by cigarette smoke exposure，and regulation by miRNA may be a potential mechanism of Chinese medicinal in the treatment of COPD.

Keywords Differentially expressed gene; Chronic obstructive pulmonary disease; miRNA; Chinese medicinal; Cigarette smoke

中图分类号：R282;R563文献标识码：Adoi：10.3969/j.issn.1673-7202.2021.14.023

慢性阻塞性肺疾病（Chronic Obstructive Pulmoriary Disease，COPD）是以持续性呼吸道症状和气流受限为主要特征的一种呼吸系统常见病，感染是诱发COPD急性加重的主要原因，香烟烟雾则是COPD最重要的独立危险因素[1]。COPD是全球第4大死因，根据2020年COPD全球创议（Global Initiative for Chronic Obstructive Lung Disease）可知，随着发展中国家吸烟率的升高和高收入国家老龄化加剧，COPD的发病率在未来40年仍会继续上升，至2060年可能每年有超过540万人死于COPD及其相关疾病[2]。目前COPD的基础治疗用药为吸入性支气管扩张剂，而在COPD的防治过程中，戒烟的重要性越来越得到认可。……