基于网络药理学和分子对接探讨抵挡汤抗肺纤维化作用机制研究

Study on Anti-Pulmonary Fibrosis Mechanism of Didang Decoction Based on Network Pharmacology and Molecular Docking

抵挡汤具有治疗肺部纤维化的作用,但其作用机制尚不明确,本文基于网络药理学和分子对接探讨抵挡汤抗肺纤维化的作用机制。运用TCMSP数据库和BATMAN数据库筛选出抵挡汤的活性成分和靶点,在GeneCards、OMIM、TTD数据库中获得疾病相关靶点,通过Venny 2.1在线平台制作Venny图获得抵挡汤与肺纤维化的交集靶点,再利用Cytoscape软件构建药物–活性化合物–靶点网络,String数据库构建 PPI网络,利用Metascape数据库对交集靶点进行富集分析,最后选取关键靶点对抵挡汤的关键成分进行分子对接验证。研究得到抵挡汤活性成分60个,交集基因共有454个,蛋白互作分析得到核心作用靶点有AKT1、EP300、SRC等,GO分析富集显示相关生物过程涉及基因表达的正向调控、对药物反应、对RNA聚合酶II启动子转录的正向调控等,KEGG富集结果显示主要通路涉及癌症通路、AGE-RAGE信号通路、人巨细胞病毒感染等。研究结果表明抵挡汤抗肺纤维化具有多成分、多靶点、多通路协同调节的特点,为其后期作用机制研究奠定了基础。

Didang Decoction has the effect of treating pulmonary fibrosis, but its mechanism of action is not clear. Based on network pharmacology and molecular docking, this paper discusses the mechanism of Didang Decoction against pulmonary fibrosis. The active ingredients and targets of antisepsis decoction were screened using TCMSP and BATMAN databases, disease-related targets were obtained from GeneCards, OMIM and TTD databases, and the intersection targets of antisepsis decoction and pulmonary fibrosis were obtained by making Venny diagram through Venny 2.1 online platform. Cytoscape software was used to construct a drug-active compound-target network, String database was used to construct a PPI network, Metascape database was used for enrichment analysis of intersection targets, and finally, key targets were selected for molecular docking verification.60 active components of the decoction were obtained, including 454 overlapping genes. Protein interaction analysis showed that the core targets were AKT1, EP300, SRC, etc. GO analysis enrichment showed that the related biological processes involved positive regulation of gene expression, drug response, and RNA polymerase II promoter transcription. KEGG enrichment results showed that the major pathways involved the cancer pathway, AGE-RAGE signaling pathway and human cytomegalovirus infection. The results showed that Didang Decoction has the characteristics of multi-component, multi-target and multi-pathway synergistic regulation, which laid the foundation for the later study of its mechanism of action.