目的 通過(guò)數(shù)據(jù)挖掘《普濟(jì)方》中治療類風(fēng)濕關(guān)節(jié)炎（RA）相關(guān)方劑用藥規(guī)律及組方特點(diǎn)，并利用網(wǎng)絡(luò)藥理學(xué)分析核心藥對(duì)抗RA的作用機(jī)制。方法 檢索《中華醫(yī)典》電子圖書(shū)系統(tǒng)搜集《普濟(jì)方》中治療RA的方劑，并利用Excel軟件統(tǒng)計(jì)中藥性味、歸經(jīng)、功效等，使用R語(yǔ)言對(duì)頻數(shù)、中藥關(guān)聯(lián)規(guī)則及聚類規(guī)律進(jìn)行分析?；跀?shù)據(jù)挖掘結(jié)果得到核心藥對(duì)，利用中藥系統(tǒng)藥理學(xué)數(shù)據(jù)庫(kù)與分析平臺(tái)（TCMSP）、Pharmmapper、STRING等數(shù)據(jù)庫(kù)，R語(yǔ)言、Cytoscape軟件構(gòu)建“藥對(duì)-成分-靶點(diǎn)-疾病”和蛋白質(zhì)-蛋白質(zhì)相互作用（PPI）網(wǎng)絡(luò)，對(duì)核心藥對(duì)抗 RA靶點(diǎn)進(jìn)行功能富集分析。結(jié)果 《普濟(jì)方》中共搜集出601首治療RA的方劑，321味中藥。頻次≥40高頻中藥（肉桂、防風(fēng)、附子、當(dāng)歸、甘草、川芎、羌活等）以溫性、辛味為主，多歸脾、腎經(jīng)，功效主要以補(bǔ)虛、解表、溫里最為常見(jiàn)。高頻中藥關(guān)聯(lián)規(guī)則得到 17組藥對(duì)組合（“獨(dú)活-防風(fēng)”置信度最高為核心藥對(duì)），系統(tǒng)聚類得到4組類聚方。利用各數(shù)據(jù)庫(kù)獲取“獨(dú)活-防風(fēng)”活性成分24個(gè)、306個(gè)靶點(diǎn)以及RA相關(guān)靶點(diǎn)3 964個(gè)，產(chǎn)生交集靶點(diǎn)173個(gè)。網(wǎng)絡(luò)分析結(jié)果表明當(dāng)歸內(nèi)酯、亞麻油酸乙酯、當(dāng)歸醇、谷甾醇等可能是抗RA的主要活性成分，關(guān)鍵靶點(diǎn)包括ALB、HSP90AA1、MMP9、EGFR等，可能通過(guò)調(diào)控Ras信號(hào)通路、P13K-Akt信號(hào)通路、FoXO信號(hào)通路和MAPK信號(hào)通路等發(fā)揮抗RA作用。結(jié)論 《普濟(jì)方》抗RA方劑中藥多為溫辛、歸脾腎及補(bǔ)虛之類，網(wǎng)絡(luò)藥理學(xué)結(jié)果顯示核心藥對(duì)“獨(dú)活-防風(fēng)”可能通過(guò)調(diào)控多靶點(diǎn)、多通路發(fā)揮治療作用。

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

南京藥學(xué)會(huì)-常州四藥醫(yī)院藥學(xué)科研基金項(xiàng)目（2022YX005）