基于生物信息学方法探讨肠道菌群干预类风湿关节炎的机制及药物预测  

Mechanism and drug prediction of intestinal flora intervention in rheumatoid arthritis based on bioinformatics

作　　者：卜尔凡 张钏海 于臻祎 伍嘉琪 刘良 潘胡丹 BU Erfan;ZHANG Chuanhai;YU Zhenyi;WU Jiaqi;LIU Liang;PAN Hudan(Faculty of Chinese Medicine,Macao University of Science and Technology(M.U.S.T.),Macao 999078,China;State Key Laboratory of Traditional Chinese Medicine Syndrome,the Second Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405,China)

机构地区：[1]澳门科技大学中医药学院,中国澳门999078 [2]广州中医药大学第二附属医院中医证候全国重点实验室,广州510405

出　　处：《中国免疫学杂志》2025年第3期522-528,共7页Chinese Journal of Immunology

基　　金：国家自然科学基金项目(82230119);省部共建中医湿证国家重点实验室开放课题(SZ2022KF03);澳门科学技术发展基金项目(0010/2020/A1);广东省基础与应用基础项目(2020B1515130005)。

摘　　要：目的:探究肠道菌群紊乱与类风湿关节炎(RA)的诊断及治疗应答的相关性,为精准靶向干预RA的进一步研究提供生物信息学依据。方法:从疾病数据库中分别下载并筛选整合肠道菌群紊乱疾病相关基因与RA基因,应用生物信息学方法对两种疾病的相关性进行综合分析,通过STRING和Cytoscape及其插件分析PPI网络,筛选关键基因。将关键基因映射至CoremineMedicinal中得到相对应的化学药物及中药。结果:通过对疾病数据库的整合筛选,共获得525个肠道菌群紊乱与RA的共有基因,最终选取蛋白相互作用程度最强的基因为关键基因,分别为IL-6、IL-1β、TNF-α、IL-10、STAT3、STAT1、RE-LA。这些相关基因主要涉及负反馈调节、抗原刺激等生物过程,介导脂多糖受体结合、NF-κB受体结合等分子功能,主要富集在质膜区域;KEGG分析显示这些相关基因主要涉及IL-17通路、Toll样受体通路等经典信号通路。通过药物预测,发现了一些重组细胞因子及中药黄芪、黄芩、五味子、黄连等可能成为治疗RA的潜在药物来源。结论:生物信息学方法可预测肠道菌群干预RA发病,发现相关基因和信号通路,并预测可能通过靶向调控菌群治疗RA的中草药,为深入探讨靶向治疗RA提供了理论依据。Objective:To explore the correlation between intestinal flora disturbance and the diagnosis,treatment of rheumatoid arthritis(RA),and to provide bioinformatics basis for further research on precise targeted intervention of RA.Methods:Genes related to intestinal flora disorders and RA genes were downloaded from disease database.Correlation between the two diseases was analyzed via bioinformatics approach.PPI network was conducted by STRING,Cytoscape and their plug-ins,and key genes were screened.Key genes were mapped into Coremine Medicinal to identify medicinal chemicals and medicinal herbs.Results:A total of 525 genes shared by intestinal flora disorders and RA were obtained through integrated screening of the disease database,and key genes with the highest degree of protein interaction were finally selected,namely IL-6,IL-1β,TNF-α,IL-10,STAT3,STAT1 and RELA.These related targeted genes were mainly involved in biological processes such as negative feedback regulation and antigen stimulation,and mediate molecular functions such as lipopolysaccharide receptor binding and NF-κB receptor binding,which are mainly concentrated in the plasma membrane region.KEGG analysis showed that these related genes were mainly involved in classical signaling pathways such as IL-17 pathway and Toll-like receptor pathway.Through drug prediction,it was found that Astragalus,Scutellaria,Schisandra and Coptis in traditional Chinese medicine might be potential drug sources for RA treatment.Conclusion:Bioinformatics method can predict key genes and signaling pathways of intestinal flora intervention in pathogenesis and progression of RA,and predict the Chinese herbs that may target the regulation of flora for treatment of risk factors,which providing a theoretical basis for further exploration of targeted treatment of RA.

关 键 词：生物信息学 类风湿关节炎 肠道菌群紊乱 药物预测 靶点蛋白 

分 类 号：R392[医药卫生—免疫学]