【目的】 探讨舒筋洗外用颗粒治疗骨关节炎的潜在靶点及作用机制。【方法】 从TCMSP、TCMIP、TCMID和HERB数据库 中收集舒筋洗外用颗粒的化学成分及其靶点，从GEO数据库获取骨关节炎的相关靶基因。筛选共同靶点，利用Cytoscape软件构 建“舒筋洗外用颗粒-化合物-骨关节炎-靶点”互作网络和“蛋白-蛋白”互作网络。通过DAVID数据库对交集靶点进行基 因本体论（GO）和京都基因与基因组百科全书（KEGG）途径富集分析，选择度值最高的化合物和蛋白质，利用 AutoDock Vina 进行分子对接。【结果】 舒筋洗外用颗粒中共有85个成分，915个靶点。获得骨关节炎的作用靶点4 383个。舒筋洗外用颗粒 与骨关节炎共有靶点248个。关键的靶蛋白有表皮生长因子受体（EGFR）、周期蛋白依赖性激酶1（CDK1）、基质金属蛋白酶 9（MMP9），关键化合物有 N-反式阿魏酰酪胺、黄藤素、蛇菰宁、金色酰胺醇酯、Saroaspidin A、木犀草素、五味子素、钩 藤碱、钩藤碱A、山柰酚、胡椒碱。GO功能富集分析获得了489个生物过程、162个细胞成分和87个分子功能，KEGG途径 富集分析获得100个与舒筋洗外用颗粒治疗相关的信号通路。分子对接结果表明，N-反式阿魏酰酪胺、胡椒碱和钩藤碱 A 分别与关键靶点EGFR、CDK1和MMP9具有良好的结合能力。【结论】 舒筋洗外用颗粒可能通过N-反式阿魏酰酪胺、钩藤碱A、 胡椒碱等关键有效成分与癌症通路、缺氧诱导因子 1（HIF-1）通路和钙离子信号通路等中的关键靶点 EGFR、CDK1 以及 MMP9相结合，发挥治疗骨关节炎的效果。

Objective To explore the potential therapeutic targets and mechanisms of Shujinxi External Granules in the treatment of osteoarthritis（OA）. Methods The chemical constituents and targets of Shujinxi External Granules were collected from TCMSP，TCMIP，TCMID and HERB databases，and the target genes related to OA were obtained from GEO database. Screening the overlapping targets， Cytoscape software was used to construct the “Shujinxi External Granules-compounds-OA-targets” and protein-protein interaction （PPI） networks. Gene Ontology（GO）analysis and Kyoto Encyclopedia of Genes and Genomes（KEGG）pathway enrichment analysis were performed on the overlapping targets through DAVID database， and the compounds and proteins with the highest degree values were selected for molecular docking by using AutoDock Vina. Results There were 85 components and 915 targets were found in Shujinxi External Granules. The 4 383 targets of OA were obtained， and 248 overlapping targets were screened out between Shujinxi External Granules and OA. The key target proteins were epidermal growth factor receptor（EGFR），cyclin-dependent kinase 1（CDK1），matrix metalloproteinase 9（MMP9）， and the key compounds were N-trans-feruloyltyramine， palmatine， balanophonin， aurantiamide acetate， Saroaspidin A， luteolin， schizandrin， rhynchophylline， rhynchophylline A， kaempferol， 1- piperoylpiperidine. A total of 489 biological processes，162 cellular components and 87 molecular functions were obtained by using GO functional enrichment analysis， and 100 signaling pathways related to the therapeutic of Shujinxi External Granules were obtained by using KEGG pathway enrichment analysis. The molecular docking results showed that N-trans-feruloyltyramine， 1-piperonoylpiperidine and rhynchophylline A had good binding ability to the key targets EGFR，CDK1 and MMP9，respectively. Conclusion The Shujinxi External Granules may bind to the key targets EGFR，CDK1，and MMP9 in the pathways in cancer，hypoxia-inducible factor 1（HIF-1） and calcium signaling pathway through the key active components， such as N-trans-feruloyltyramine， rhynchophylline A，and 1-piperoylpiperidine，to exert the therapeutic effects on OA.

R285.5

中国博士后科学基金项目（编号：2022M720731）；广东省基础与应用基础研究基金项目（编号：2021A1515110142）