目的 运用网络药理学和分子对接技术探讨冬虫夏草干预慢性阻塞性肺疾病的物质基础及作用机制。方法 通过TCMSP等数据库筛选冬虫夏草活性成分并预测其作用靶点。采用GeneCards、OMIM数据库筛选慢性阻塞性肺疾病靶点，合并后去重，与活性成分靶点取交集。运用String数据库构建交集靶点的蛋白质相互作用（PPI）网络图，利用Cytoscape 3.8.2软件进行拓扑分析和可视化处理。采用Metascape数据库对核心靶点进行基因本体（GO）功能富集分析和与京都基因与基因组百科全书（KEGG）通路富集分析。运用SwissDock、Pymol软件进行分子对接验证。结果 筛选得到冬虫夏草14个主要活性成分，包括花生四烯酸、啤酒甾醇、β-谷甾醇、麦角醇、黄豆黄素、棕榈酸胆固醇酯、胆固醇、乙酸亚油酯、豆甾醇、过氧麦角甾醇、菜油甾醇、腺苷、D-甘露醇和麦角甾醇。冬虫夏草活性成分与慢性阻塞性肺疾病相关的交集靶点有91个，核心靶点为肿瘤坏死因子（TNF）、肿瘤蛋白p53（TP53）、半胱氨酸天冬氨酸蛋白酶-3（CASP3）、表皮生长因子受体（EGFR）、基质金属蛋白酶9（MMP9）、非受体蛋白酪氨酸激酶（SRC）等。GO和KEGG分析结果显示，冬虫夏草干预慢性阻塞性肺疾病的作用机制主要涉及癌症通路、癌症相关蛋白聚糖、脂质和动脉粥样硬化通路、Ca²⁺信号通路、VEGF信号通路、TRP通道的炎症介质调节通路等。分子对接结果显示，冬虫夏草活性成分啤酒甾醇与核心靶点MMP9具有较高亲和力。结论 本研究发现冬虫夏草可能通过其有效成分花生四烯酸、啤酒甾醇、β-谷甾醇、棕榈酸胆固醇酯、乙酸亚油酯、腺苷、麦角甾醇等作用于TNF、TP53、CASP3、EGFR、MMP9、SRC等慢性阻塞性肺疾病相关靶点，通过调控癌症通路、癌症相关蛋白聚糖等发挥干预慢性阻塞性肺疾病的作用。

Objective To explore the material basis and mechanism of Cordyceps sinensis in treatment of chronic obstructive pulmonary disease based on network pharmacology and molecular docking techniques. Methods TCMSP and other databases were used to screen the active ingredients of Cordyceps sinensis and predict their targets. GeneCards and OMIM databases were used to screen chronic obstructive pulmonary disease targets. After merging and deduplicating, the intersection with the active ingredient targets was taken. PPI network of intersection targets was constructed using String database, and the topology analysis and visualization were performed using Cytoscape 3.8.2 software. The Metascape database was used to perform GO functional enrichment analysis and KEGG pathway enrichment analysis of the core targets. Finally, Molecular docking verification was performed using SwissDock and Pymol software. Results 14 Active components were selected from Cordyceps sinensis, including arachidonic acid, cerevisterol, beta-sitosterol, lysergol, glycitein, cholesteryl palmitate, cholesterol, linoleyl acetate, stigmasterol, peroxyergosterol, campesterol, adenosine, D-mannitol, and ergosterol. There were 91 intersecting targets of Cordyceps sinensis ingredients associated with chronic obstructive pulmonary disease disease, involving TNF, TP53, CASP3, EGFR, MMP9, and SRC. GO and KEGG analysis results showed that the mechanism of Cordyceps sinensis intervention in chronic obstructive pulmonary disease mainly involved pathways in cancer, proteoglycans in cancer, lipid and atherosclerosis, calcium signaling pathway, VEGF signaling pathway, inflammatory mediator regulation of TRP channels. Molecular docking results demonstrated that cerevisterol, the core active components of Cordyceps sinensis, has a highest affinity with MMP9. Conclusion In this study, it was found that Cordyceps sinensis may act on the disease related targets of TNF, TP53, CASP3, EGFR, MMP9, and SRC through its active components, such as arachidonic acid, brewer sterol, β-sitosterol, cholesterol palmitate, linoleate acetate, adenosine and ergosterol. By regulating cancer pathways, cancer-related proteoglycans play a role in the intervention of chronic obstructive pulmonary disease.

R285;R286.4

青海省科技计划项目（2021-SF-A4）；青海省人民政府三江源国家公园联合专项（LHZX-2022-01）；青海省“中青年人才托举工程”项目（2022QHSKXRCTJ35）