基于数据挖掘和网络药理学类风湿关节炎湿热痹阻型用药规律和作用机制分析

Analysis of Medication Law and Mechanism of Damp-heat Obstruction in Rheumatoid Arthritis Based on Data Mining and Network Pharmacology

目的基于数据挖掘与网络药理学分析期刊与专利文献中治疗类风湿关节炎湿热痹阻型方剂的用药配伍规律及作用机制。方法筛选中国知网、维普、万方等资源中近20年治疗类风湿关节炎湿热痹阻型的方剂,通过中医传承辅助平台软件构建方剂数据库,利用该软件集成的关联规则及熵聚类等数据挖掘算法,总结治疗类风湿关节炎湿热痹阻型方剂中的用药规律、核心药物配伍及发现新方,在运用中药系统药理学数据库与分析平台(traditional chinese medicine systems pharmacology database and analysis platform,TCMSP)、Cytoscape等数据库对其核心药物进行信号通路(kyoto encyclopedia of genes and genomes,KEGG)分析,构建靶基因-信号通路关系网络。结果通过对81首治疗类风湿关节炎湿热痹阻型方剂所含药物的频次统计分析,得到常用药物32味,其中薏苡仁、黄柏使用频次最高;四气统计以寒、温、平为主;五味统计主要以苦、甘、辛为主;归经统计主要归为肝、脾、胃经;使用频次较高的药对24个,其中黄柏、薏苡仁与黄柏、苍术居前2位;基于复杂系统熵聚类,演化出3味药的核心组合共计42个;通过无监督的熵层次聚类算法得到11首新处方;对核心药对黄柏、薏苡仁进行网络药理学分析前10位靶点基因分别是IL-6、MMP3、CCND1、MMP1、CXCL10、MMP9、FOS、SPP1、VEGFA、PTGS2;KEGG富集通路主要富集在IL-17信号通路、TNF信号通路、Toll样受体信号转导等信号通路。结论治疗类风湿关节炎湿热痹阻型的方剂多以清热、利水燥湿、祛风湿、通络止痛为主,其核心药物配伍活性成分主要通过干扰IL-6、MMP3等靶基因及调节IL-17等信号通路来治疗类风湿关节炎。

Objective Based on data mining and network pharmacology analysis of the compatibility and mechanism of prescriptions for the treatment of rheumatoid arthritis in journals and patent literature. Methods Screening prescriptions for the treatment of rheumatoid arthritis with damp-heat obstruction in recent 20 years from China knowledge Network,VIP,WanFang and other resources,constructing prescription database through TCM inheritance auxiliary platform software,using association rules and entropy clustering and other data mining algorithms integrated by the software,summarize the rules of drug use,core drug compatibility and discovery of new prescriptions in the treatment of rheumatoid arthritis. In the use of traditional Chinese medicine system pharmacology database(TCMSP),Cytoscape and other databases to analyze the signal pathway of its core drugs,and construct the target gene-signal pathway relationship network. Results Through the statistical analysis of the frequency of 81 prescriptions for the treatment of rheumatoid arthritis with dampness-heat obstruction,32 commonly used drugs were obtained,among which Yiyiren(Coicis Semen)and Huangbai(Phellodendri Chinensis Cortex)were used most frequently,and the statistics of four Qi were mainly cold,warm and flat;the statistics of five flavors were mainly bitter,sweet and pungent;the statistics of meridians were mainly classified into liver,spleen and stomach meridians,and 24 frequently used drugs were used,of which Huangbai(Phellodendri Chinensis Cortex) and Yiyiren(Coicis Semen),Huangbai(Phellodendri Chinensis Cortex) and Cangzhu(Atractylodis Rhizoma)ranked in the top 2. Based on complex system entropy clustering,a total of 42 core combinations of three drugs were evolved,and 11 new prescriptions were obtained by unsupervised entropy hierarchical clustering algorithm. Based on the network pharmacological analysis of Huangbai(Phellodendri Chinensis Cortex)and Yiyiren(Coicis Semen),the top ten target genes are IL-6,MMP3,CCND1,MMP1,CXCL10,MMP9,FOS,SPP1,VEGFA and PTGS2. KEGG enrichment pathway is mainly concentrated in IL-17 signal pathway,TNF signal pathway,Toll-like receptor signal transduction and other signal pathways. Conclusion The prescriptions for the treatment of rheumatoid arthritis of dampness-heat obstruction type are mainly heat-clearing,diuresis-dryness-dampness,dispelling rheumatism,dredging collaterals and relieving pain,and its core drug compatibility active components mainly treat rheumatoid arthritis by interfering with IL-6,MMP3 and other target genes and regulating IL-17 and other signal pathways.