基于数据挖掘与网络药理学探究中医药治疗肺纤维化用药规律及作用机制

Analysis of Medication Rules and Mechanisms of Chinese Medicinals in Treatment of Pulmonary Fibrosis Based on Data Mining and Network Pharmacology

目的 基于数据挖掘与网络药理学探究中医药治疗肺纤维化中药配伍规律及潜在作用机制。方法 检索中国知网、万方数据库、维普数据库中近10年来治疗肺纤维化的方剂,依据限定条件整理后,采用IBM SPSS Modeler18、IBM SPSS Statistics 20软件分析药物组方规律、关联规则,归纳中药治疗肺纤维化用药规律及药物配伍;并通过中药系统药理学数据库(TCMSP)获取核心配伍药物的活性成分及靶点,GeneCards数据库获取肺纤维化的潜在作用靶点,并将疾病与药物交集靶点导入STRING 11.0和Cytoscape 3.8.0获取核心靶点,对交集靶点进一步进行基因本体(gene ontology,GO)和京都基因与基因组百科全书(kyoto encylopaedia of genes and genomes,KEGG)富集分析,取前20条通路,通过Cytoscape 3.8.0构建“药物-成分-靶点-通路”网络。结果 通过检索文献,筛选总结出治疗肺纤维化方剂158个,中药195个,使用频率前5的药物即黄芪、丹参、甘草、当归、川芎;关联规则数据显示黄芪-党参-丹参支持度与置信度最高,聚类分析将中药分为5类。对“黄芪-丹参-党参”进行网络药理学分析,获取核心药对与肺纤维化交集靶点54个,核心靶点12个:JUN、TP53、AKT1、MAPK1等,涉及通路246条,主要包括癌症通路(Pathways in cancer)、凋亡(Apoptosis)通路、PI3K-Akt信号通路等。结论 核心药对主要活性成分可能通过JUN、IL-6等靶点参与PI3K-Akt、TNF等信号通路以抑制胶原蛋白沉积及成纤维细胞增殖,起到延缓肺纤维化发展的作用,为中医药改善患者肺纤维化症状,延缓疾病发展提供数据支持及理论依据。

Objective To investigate the pattern of Chinese medicine formulas and potential mechanisms of action in the treatment of pulmonary fibrosis based on data mining and network pharmacology.Methods The prescriptions for the treatment of pulmonary fibrosis in the past 10 years were retrieved from China Knowledge Network,WanFang database,and Vipshop database,and then organized according to the qualifying conditions,and IBM SPSS Modeler 18 and IBM SPSS Statistics 20 software were used to analyze the drug grouping rules and association rules,and summarize the drug use rules and drug combinations in the treatment of pulmonary fibrosis in Chinese medicine;and the active ingredients and targets of the core drug combinations were obtained from the TCMSP database,and the potential targets of pulmonary fibrosis were obtained from the GeneCards database,and the disease and drug intersection targets were imported into STRING 11.0 and Cytoscape 3.8.0 to obtain the core targets,and the intersection targets were further subjected to Gene Ontology,GO and Kyoto Encylopaedia of Genes and Genomes(KEGG)enrichment analyses were performed to obtain the top 20 pathways and construct a“drug-component-target-pathway”network by Cytoscape 3.8.0.Results By searching the literature,158 prescriptions for pulmonary fibrosis and 195 Chinese medicines were screened and summarized,and the top five drugs used were Huangqi(Astragali Radix),Danshen(Salviae Miltiorrhizae),Gancao(Glycyrrhizae Radix Et Rhizoma),Danggui(Angelicae Sinensis Radix),Chuanxiong(Chuanxiong Rhizoma).The network pharmacology analysis of“Huangqi(Astragali Radix)-Danshen(Salviae Miltiorrhizae)-Dangshen(Codonopsis Radix)”showed that 54 core drug pairs intersected with pulmonary fibrosis targets,12 core targets:JUN,TPT53,AKT1,MAPK1,etc.,involving 246 pathways,mainly including pathways in cancer,apoptosis pathway,PI3K-Akt signaling pathway,etc.Conclusion The main active ingredients of the core drug may be involved in PI3K-Akt signaling pathway,TNF signaling pathway and other signaling pathways through targets such as JUN and IL-6 to inhibit collagen deposition and fibroblast proliferation,and play a role in delaying the development of pulmonary fibrosis,which provides data and theoretical basis for TCM to improve the symptoms of pulmonary fibrosis and delay the development of the disease in patients.