目的 利用网络药理学和生物信息学探讨小檗胺治疗特发性肺纤维化的作用机制。方法 利用PharmMapper和Super-PRED数据库检索小檗胺的作用靶点，利用GeneCards数据库检索特发性肺纤维化疾病靶点，并利用GEO数据库下载GSE110147数据集，进行差异分析，获得特发性肺纤维化差异表达基因（DEGs）。上述靶点取交集获得小檗胺治疗特发性肺纤维化的潜在作用靶点。使用String数据库和Cytoscape软件进行蛋白质-蛋白质相互作用（PPI）网络分析，筛选出核心靶点。利用Metascape数据库进行富集分析，构建“成分-靶点-通路-疾病”网络图。利用Autodock Vina和Discovery Studio等软件进行分子对接和可视化。利用GeneMANIA数据库的功能关联（GMFA）网络分析进一步丰富网络药理学研究内容。结果 共获得32个小檗胺治疗特发性肺纤维化的潜在作用靶点，基因本体（GO）功能主要与细胞迁移、伤口愈合以及激酶调节相关，京都基因与基因组百科全书（KEGG）通路主要富集在表皮生长因子受体（EGFR）酪氨酸激酶抑制剂耐药、磷脂酰肌醇激酶/蛋白激酶B（PI3K/Akt）信号通路、叉头盒转录因子（FoxO）信号通路等。核心靶点为半胱天冬蛋白酶-3（CASP3）、胰岛素样生长因子1（IGF1）、缺氧诱导因子1亚基α（HIF1A）、磷脂酰肌醇4,5-二磷酸3-激酶催化亚基α（PIK3CA），均与小檗胺具有良好结合能力。结论 通过网络药理学结合生物信息学，辅以GMFA网络分析和分子对接验证，揭示小檗胺可能通过多靶点和多通路发挥治疗特发性肺纤维化的作用。

Objective To explore the molecular mechanism of berbamine in treatment of idiopathic pulmonary fibrosis by network pharmacology and bioinformatics. Methods The related targets of berbamine were retrieved by PharmMapper and Super-PRED databases, and the related targets of idiopathic pulmonary fibrosis were retrieved by GeneCards database. The GSE110147 dataset was download by GEO database, and the differential expression genes (DEGs) of idiopathic pulmonary fibrosis were obtained by differential analysis. The potential target genes of berbamine against idiopathic pulmonary fibrosis were obtained by intersection. Protein-protein interaction (PPI) network analysis was performed using String database and Cytoscape software to identify the core targets. Metascape was used for enrichment analysis, and construct a “component-target-pathway-disease” network diagram. Molecular docking was performed using Autodock Vina and Discovery Studio software. The GeneMANIA-based functional association (GMFA) was used to further enrich the results of network pharmacology research. Results A total of 32 potential targets of berbamine against idiopathic pulmonary fibrosis were obtained. GO function were mainly related to cell migration, wound healing and regulation of kinase activity, and KEGG pathway were mainly enriched in EGFR tyrosine kinase inhibitor resistance, PI3K/Akt signaling pathway, FoxO signaling pathway and so on. The core targets CASP3, IGF1, HIF1A, and PIK3CA have good binding ability with berbamine. Conclusion Through network pharmacology combined with bioinformatics, supplemented by GMFA network analysis and molecular docking, it is revealed that berbamine may play a role against idiopathic pulmonary fibrosis through multiple targets and multiple pathways.

R286.4

国家自然科学基金资助项目（32060576）；广西中医药大学“桂派杏林青年英才”项目（2022C026）