目的 運(yùn)用網(wǎng)絡(luò)藥理學(xué)和分子對接技術(shù)探討冬蟲夏草干預(yù)慢性阻塞性肺疾病的物質(zhì)基礎(chǔ)及作用機(jī)制。方法 通過TCMSP等數(shù)據(jù)庫篩選冬蟲夏草活性成分并預(yù)測其作用靶點。采用GeneCards、OMIM數(shù)據(jù)庫篩選慢性阻塞性肺疾病靶點，合并后去重，與活性成分靶點取交集。運(yùn)用String數(shù)據(jù)庫構(gòu)建交集靶點的蛋白質(zhì)相互作用（PPI）網(wǎng)絡(luò)圖，利用Cytoscape 3.8.2軟件進(jìn)行拓?fù)浞治龊涂梢暬幚?。采用Metascape數(shù)據(jù)庫對核心靶點進(jìn)行基因本體（GO）功能富集分析和與京都基因與基因組百科全書（KEGG）通路富集分析。運(yùn)用SwissDock、Pymol軟件進(jìn)行分子對接驗證。結(jié)果 篩選得到冬蟲夏草14個主要活性成分，包括花生四烯酸、啤酒甾醇、β-谷甾醇、麥角醇、黃豆黃素、棕櫚酸膽固醇酯、膽固醇、乙酸亞油酯、豆甾醇、過氧麥角甾醇、菜油甾醇、腺苷、D-甘露醇和麥角甾醇。冬蟲夏草活性成分與慢性阻塞性肺疾病相關(guān)的交集靶點有91個，核心靶點為腫瘤壞死因子（TNF）、腫瘤蛋白p53（TP53）、半胱氨酸天冬氨酸蛋白酶-3（CASP3）、表皮生長因子受體（EGFR）、基質(zhì)金屬蛋白酶9（MMP9）、非受體蛋白酪氨酸激酶（SRC）等。GO和KEGG分析結(jié)果顯示，冬蟲夏草干預(yù)慢性阻塞性肺疾病的作用機(jī)制主要涉及癌癥通路、癌癥相關(guān)蛋白聚糖、脂質(zhì)和動脈粥樣硬化通路、Ca²⁺信號通路、VEGF信號通路、TRP通道的炎癥介質(zhì)調(diào)節(jié)通路等。分子對接結(jié)果顯示，冬蟲夏草活性成分啤酒甾醇與核心靶點MMP9具有較高親和力。結(jié)論 本研究發(fā)現(xiàn)冬蟲夏草可能通過其有效成分花生四烯酸、啤酒甾醇、β-谷甾醇、棕櫚酸膽固醇酯、乙酸亞油酯、腺苷、麥角甾醇等作用于TNF、TP53、CASP3、EGFR、MMP9、SRC等慢性阻塞性肺疾病相關(guān)靶點，通過調(diào)控癌癥通路、癌癥相關(guān)蛋白聚糖等發(fā)揮干預(yù)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

青海省科技計劃項目（2021-SF-A4）；青海省人民政府三江源國家公園聯(lián)合專項（LHZX-2022-01）；青海省“中青年人才托舉工程”項目（2022QHSKXRCTJ35）