目的 利用網(wǎng)絡(luò)藥理學(xué)和生物信息學(xué)探討小檗胺治療特發(fā)性肺纖維化的作用機制。方法 利用PharmMapper和Super-PRED數(shù)據(jù)庫檢索小檗胺的作用靶點，利用GeneCards數(shù)據(jù)庫檢索特發(fā)性肺纖維化疾病靶點，并利用GEO數(shù)據(jù)庫下載GSE110147數(shù)據(jù)集，進(jìn)行差異分析，獲得特發(fā)性肺纖維化差異表達(dá)基因（DEGs）。上述靶點取交集獲得小檗胺治療特發(fā)性肺纖維化的潛在作用靶點。使用String數(shù)據(jù)庫和Cytoscape軟件進(jìn)行蛋白質(zhì)-蛋白質(zhì)相互作用（PPI）網(wǎng)絡(luò)分析，篩選出核心靶點。利用Metascape數(shù)據(jù)庫進(jìn)行富集分析，構(gòu)建“成分-靶點-通路-疾病”網(wǎng)絡(luò)圖。利用Autodock Vina和Discovery Studio等軟件進(jìn)行分子對接和可視化。利用GeneMANIA數(shù)據(jù)庫的功能關(guān)聯(lián)（GMFA）網(wǎng)絡(luò)分析進(jìn)一步豐富網(wǎng)絡(luò)藥理學(xué)研究內(nèi)容。結(jié)果 共獲得32個小檗胺治療特發(fā)性肺纖維化的潛在作用靶點，基因本體（GO）功能主要與細(xì)胞遷移、傷口愈合以及激酶調(diào)節(jié)相關(guān)，京都基因與基因組百科全書（KEGG）通路主要富集在表皮生長因子受體（EGFR）酪氨酸激酶抑制劑耐藥、磷脂酰肌醇激酶/蛋白激酶B（PI3K/Akt）信號通路、叉頭盒轉(zhuǎn)錄因子（FoxO）信號通路等。核心靶點為半胱天冬蛋白酶-3（CASP3）、胰島素樣生長因子1（IGF1）、缺氧誘導(dǎo)因子1亞基α（HIF1A）、磷脂酰肌醇4,5-二磷酸3-激酶催化亞基α（PIK3CA），均與小檗胺具有良好結(jié)合能力。結(jié)論 通過網(wǎng)絡(luò)藥理學(xué)結(jié)合生物信息學(xué)，輔以GMFA網(wǎng)絡(luò)分析和分子對接驗證，揭示小檗胺可能通過多靶點和多通路發(fā)揮治療特發(fā)性肺纖維化的作用。

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

國家自然科學(xué)基金資助項目（32060576）；廣西中醫(yī)藥大學(xué)“桂派杏林青年英才”項目（2022C026）