目的 通过数据挖掘《普济方》中治疗类风湿关节炎（RA）相关方剂用药规律及组方特点，并利用网络药理学分析核心药对抗RA的作用机制。方法 检索《中华医典》电子图书系统搜集《普济方》中治疗RA的方剂，并利用Excel软件统计中药性味、归经、功效等，使用R语言对频数、中药关联规则及聚类规律进行分析。基于数据挖掘结果得到核心药对，利用中药系统药理学数据库与分析平台（TCMSP）、Pharmmapper、STRING等数据库，R语言、Cytoscape软件构建“药对-成分-靶点-疾病”和蛋白质-蛋白质相互作用（PPI）网络，对核心药对抗 RA靶点进行功能富集分析。结果 《普济方》中共搜集出601首治疗RA的方剂，321味中药。频次≥40高频中药（肉桂、防风、附子、当归、甘草、川芎、羌活等）以温性、辛味为主，多归脾、肾经，功效主要以补虚、解表、温里最为常见。高频中药关联规则得到 17组药对组合（“独活-防风”置信度最高为核心药对），系统聚类得到4组类聚方。利用各数据库获取“独活-防风”活性成分24个、306个靶点以及RA相关靶点3 964个，产生交集靶点173个。网络分析结果表明当归内酯、亚麻油酸乙酯、当归醇、谷甾醇等可能是抗RA的主要活性成分，关键靶点包括ALB、HSP90AA1、MMP9、EGFR等，可能通过调控Ras信号通路、P13K-Akt信号通路、FoXO信号通路和MAPK信号通路等发挥抗RA作用。结论 《普济方》抗RA方剂中药多为温辛、归脾肾及补虚之类，网络药理学结果显示核心药对“独活-防风”可能通过调控多靶点、多通路发挥治疗作用。

Objective Through data mining, the medication rules and prescription characteristics of relevant prescriptions for the treatment of rheumatoid arthritis (RA) in Puji Fang were analyzed, and the mechanism of action of core drugs against RA was analyzed by network pharmacology. Methods The prescriptions for RA in Puji Fang were collected by searching the electronic book system of Chinese Medical Dictionary, and Excel software was used to calculate the properties, tastes, meridian-tropism and efficacy. The frequency, association rules and clustering rules of traditional Chinese medicine were analyzed by R language. Based on the data mining results, the core drug pair was obtained, and the Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), Pharmmapper, String and other databases were used to construct the "drug-component-target-disease" and protein-protein interaction (PPI) network using R language and Cytoscape software. Functional enrichment analysis of core drugs against RA targets was performed. Results A total of 601 prescriptions for RA and 321 Chinese herbs were collected in Puji Fang. High frequency Chinese herbs (Cinnamomi Cortex, Saposhnikoviae Radix, Aconiti Lateralis Radix Praeparata, Angelicae Sinensis Radix, Glycyrrhizae Radix et Rhizoma, Chuanxiong Rhizoma, Notopterygii Rhizoma et Radix, etc.) with frequency ≥ 40 were mainly warm and spicy, and mostly affected the spleen and kidney meridians. The main effects were supplementing deficiency, relieving external symptoms and warming the interior. Seventeen groups of drug pairs were obtained by high-frequency Chinese medicine association rules (with the highest confidence of "Angelicae Pubescentis Radix-Saposhnikoviae Radix" as the core drug pair), and four groups of cluster prescriptions were obtained by systematic clustering. A total of 24 active ingredients, 306 targets and 3 964 RA-related targets were obtained from each database, and 173 intersection targets were generated. Network analysis results showed that angelicone, mandenol, angelol D, sitosterol, etc. may be the main active ingredients of anti-RA, and the key targets were ALB, HSP90AA1, MMP9, EGFR, etc. It may play a role in anti-RA by regulating Ras signaling pathway, P13K-Akt signaling pathway, FoXO signaling pathway and MAPK signaling pathway. Conclusion The traditional Chinese medicines in Puji Fang for RA are mainly used for warming and xin, regulating spleen and kidney and tonifying deficiency. The results of network pharmacology show that the core drugs may play a therapeutic role in "Angelicae Pubescentis Radix-Saposhnikoviae Radix" by regulating multiple targets and pathways.

R285.5

南京药学会-常州四药医院药学科研基金项目（2022YX005）