基于网络药理学探讨三子养亲汤治疗慢性阻塞性肺疾病的作用机制

Mechanism of Sanzi Yangqin Decoction in Treatment of Chronic Obstructive Pulmonary Disease Based on Network Pharmacology

目的:运用网络药理学的研究方法探讨三子养亲汤治疗慢性阻塞性肺疾病(COPD)的作用机制。方法:利用中药系统药理学数据库与分析平台(TCMSP)对三子养亲汤中药物的化学成分、作用靶标进行检索与筛选;利用GeneCards数据库对COPD的相关靶标进行检索与筛选;取药物与疾病的交集靶点,将交集靶点输入到String数据库进行分析,构建多层次网络和蛋白质-蛋白质相互作用(PPI)网络,并对其进行基因本体(GO)富集分析和京都基因和基因组百科全书(KEGG)富集分析。结果:筛选后得出22个三子养亲汤有效成分和231个作用靶点。COPD相关基因中Relevance score大于3的基因有5737个,药物与疾病的共有靶点有115个。PPI网络分析得出,三子养亲汤治疗COPD与AKT1、MAPK1、IL6、JUN、CASP3等基因有关。GO功能富集分析和KEGG通路富集分析得到GO条目170个、KEGG通路162条。KEGG通路富集分析得出三子养亲汤治疗COPD主要通过包括Lipid and atherosclerosis和PI3K-AKT signaling pathway等通路进行调控。结论:本研究从网络药理学的方向,系统地阐述了三子养亲汤通过药物的多成分、多靶点特点对慢性阻塞性肺疾病产生作用机制,为三子养亲汤治疗慢性阻塞性肺疾病的进一步研究提供了基础。

Objective:To explore the mechanism of Sanzi Yangqin Decoction in the treatment of chronic obstructive pulmonary disease(COPD)based on network pharmacology.Methods:The chemical components and targets of the herbal medicines in the Sanzi Yingqin Decoction were searched via Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).GeneCards was searched for the targets of COPD.The common targets shared by the herbal medicines and COPD were identified and input to String for the construction of a multi-level network and a protein-protein interaction(PPI)network.Gene ontology(GO)annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment were carried out for the common targets.Results:After screening,22 effective components and 231 targets of Sanzi Yangqin Decoction were obtained.There were 5737 COPD-related genes with relevance score greater than 3.The decoction and COPD shared 115 common targets.The PPI network revealed that the treatment of COPD by Sanzi Yangqin Decoction was associated with AKT1,MAPK1,IL6,JUN,CASP3,and other genes.GO annotation and KEGG pathway enrichment predicted 170 GO terms and 162 KEGG pathways,which indicated that Sanzi Yangqin Decoction treated COPD mainly through lipid and atherosclerosis signaling pathway and PI3K-Akt signaling pathway.Conclusion:Sanzi Yangqin Decoction treats COPD through multiple components and targets.This study provides a basis for further research on the treatment of COPD by Sanzi Yangqin Decoction.