目的 基于网络药理学结合体外实验，探究金莲花Trollius chinensis黄酮抑制肺纤维化的作用机制。方法 通过TCMSP数据库获取金莲花黄酮活性成分靶点，同时采用GeneCards数据库获取肺纤维化的疾病靶点，应用Cytoscape软件，采用蛋白互作的方式，筛选金莲花黄酮治疗肺纤维化的核心靶点，并采用Metascape对核心靶点进行基因本体（gene ontology，GO）功能及京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）通路富集分析。转化生长因子-β1（transforming growth factor-β1，TGF-β1）诱导A549细胞建立体外模型，对网络药理学的研究结果进行验证。结果 筛选得到2个金莲花黄酮活性成分、153个对应的蛋白靶点及1444个肺纤维化疾病靶点，合并后得到96个核心靶点。Metascape富集分析发现，金莲花黄酮抑制肺纤维化与氧化应激密切相关，与细胞因子受体结合、细胞因子活性、受体配体活性调节等有关。KEGG通路分析显示涉及癌症途径、脂质与动脉粥样硬化、炎症响应途径等。体外实验结果表明，金莲花黄酮具有良好的体外抗氧化活性，明显抑制TGF-β1诱导的上皮间充质转化和氧化应激反应（P＜0.05、0.01、0.001），抑制信号转导分子2/3（signal transduction molecule 2/3，Smad2/3）、哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin，mTOR）及核因子-κB（nuclear factor-κB，NF-κB）激活（P＜0.001）。结论 金莲花黄酮可以通过体外抗氧化活性阻断肺纤维化进程，抑制肺纤维化发展。

Objective To explore the mechanism of Trollius chinensis flavonoids on pulmonary fibrosis based on network pharmacology combined with in vitro experiment. Methods The active component targets of T. chinensis flavonoids were obtained through TCMSP database, disease targets of pulmonary fibrosis were obtained through GeneCards database, and core targets of T. chinensis flavonoids in treatment of pulmonary fibrosis were screened by Cytoscape software and protein interaction. Metascape was used to perform gene ontology (GO) function and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis of core targets. A549 cells was induced by transforming growth factor-β1 (TGF-β1) to establish an in vitro model to verify the results of network pharmacology. Results Two flavonoid active components, 153 corresponding protein targets and 1444 pulmonary fibrosis disease targets were obtained from the screening, and 96 core targets were obtained after the combination. Metascape enrichment analysis found that the inhibition of pulmonary fibrosis by T. chinensis flavonoids was closely related to oxidative stress, and was related to cytokine receptor binding, cytokine activity, receptor ligand activity regulation, etc. KEGG pathway analysis showed that it involved cancer pathway, lipid and atherosclerosis, inflammatory response pathway, etc. The results of in vitro experiments showed that T. chinensis flavonoids had good antioxidant activity in vitro and significantly inhibited TGF-β1 induced epithelial-mesenchymal transformation and oxidative stress response (P ＜ 0.05, 0.01, 0.001), inhibited signal transduction molecule 2/3 (Smad2/3), mammalian target of rapamycin (mTOR) and nuclear factor-κB (NF-κB) activation (P ＜ 0.001).Conclusion T. chinensis flavonoids can block the process of pulmonary fibrosis and inhibit the development of pulmonary fibrosis through antioxidant activity in vitro.

R285.5

中央引导地方科技发展专项资金（YDZX2021097）；宁夏自然科学基金资助项目（2020AAC03296）；费县揭榜制组阁制项目（2022-01）；山东省自然科学基金面上项目（ZR2021MC149）