基于生物信息学探索针灸治疗类风湿关节炎关键靶标及候选中药识别

Exploring the mechanism of action of acupuncture-targeted therapy for rheumatoid arthritis and identifying candidate traditional Chinese medicines

目的根据针灸治疗类风湿关节炎关键靶标,预测共同治疗类风湿关节炎的相关中药。方法收集文献中针灸治疗类风湿关节炎疾病靶点,检索GEO数据库获得GSE205962基因芯片,使用R 4.3.1语言筛选差异表达基因,构建加权基因共表达网络(WGCNA)。将采集靶点与差异基因取交集,获得共同靶点,进行高通量GO功能和KEGG通路富集分析,使用STRING数据库和Cytoscape 3.9.0软件构建PPI网络,筛选Hub基因。使用CIBERSORT算法探究类风湿关节炎免疫浸润机制,运用Coremine Medical数据库进行中药预测。结果共筛选出8个关键靶标(RHOA、JAK1、FYN、LCK、STAT1、STAT3、EGF、GATA3)。免疫浸润分析结果显示,多种免疫细胞与类风湿关节炎的生物过程密切相关,包括γδT细胞、单核细胞、调节T细胞、CD8 T细胞等。防风、桂枝、知母、石斛、生地黄、金银花、半夏、升麻、茯苓、防己10味中药为治疗类风湿关节炎常用关键中药。结论针灸可能通过调控RHOA,JAK1,FYN,LCK等核心靶点治疗类风湿关节炎,预测中药可作为治疗类风湿关节炎的药物来源,为针药结合治疗类风湿关节炎提供思路。

Objective Exploration on the mechanism of acupuncture-targeted therapy for rheumatoid arthritis and identification of candidate Chinese materia medica.Methods Targets of acupuncture for RA were collected from related literature,and GSE205962 gene chips were obtained from GEO database.The weighted co-expression network(WGCNA)was constructed by screening differentially expressed genes using R 4.3.1.The collection targets were taken to intersect with the differential genes,and the common genes were obtained for high-throughput GO and KEGG enrichment.The Hub genes were screened by constructing protein interaction networks using the String database and Cytoscape 3.9.0 software.The CIBERSORT algorithm was used to explore the mechanisms of RA immune infiltration,and finally the Coremine Medical database was applied to predict Chinese materia medica.Results A total of 8 key targets were selected(RHOA,JAK1,FYN,LCK,STAT1,STAT3,EGF,GATA3).The results of immune infiltration analysis showed that various immune cells were closely related to the biological processes of rheumatoid arthritis,includingγδT cells,monocytes,regulatory T cells,CD8 T cells,etc.Saposheikovize Radix,Cinnamomi Ramulus,Anemarrhenae Rhizoma,Dendrobii Caulis,Rehmannine Radix,Lonicerae Japonicae Flos,Pinelliae Rhizoma,Cimicifugae Rhizoma,Poria,Stephaniae Tetrandrae Radix were the 10 kinds of commonly used key Chinese materia medica in the treatment of RA.Conclusions Acupuncture and moxibustion may treat RA by regulating RHOA,JAK1,FYN,LCK and other core targets.This study predicts that Chinese materia medica can be used as a source of drugs for the treatment of RA,and can provide new ideas for the combination of acupuncture and medicine for the treatment of RA.