基于网络药理学探讨芎归六君子汤治疗慢性阻塞性肺疾病作用机制

Study of the Molecular Mechanism of Treating COPD with Xionggui Liujunzi Fromula Based on Network Pharmacology

目的探讨芎归六君子汤治疗慢性阻塞性肺疾病(COPD)的作用机制。方法在TCMSP平台检索芎归六君子汤化学成分及靶标蛋白,以“chronic obstructive pulmonary disease”为关键词,在数据库GeneCards中检索COPD疾病靶点,并取芎归六君子汤靶标蛋白与COPD疾病靶点的交集靶点;再利用交集靶点在String上构建PPI网络,用Cytoscape 3.8.0构建中药-有效成分-靶点网络并筛选核心成分,利用Cytohubba筛选出PPI网络中的核心靶点并进行生物信息学富集分析,使用Autodock Vina对潜在药效物质与关键靶点进行分子对接。结果在TCMSP平台筛选得到芎归六君子汤有效成分154个,与之对应的靶标蛋白284个;GeneCards数据库搜索得到3854个COPD疾病靶点,与靶标蛋白交集得到163个潜在治疗靶点;对“中药-有效成分-靶点”网络分析得到10个核心有效成分;经Cytohubba筛选得到核心靶点14个,对核心靶点通过KEGG富集分析得到126条通路,GO富集分析得到635条通路。结论芎归六君子汤可能通过抑制炎性反应等途径起到治疗COPD的作用。

Objective To investigate the mechanism of Xionggui Liujunzi Fromula in treating chronic obstructive pulmonary disease(COPD)using network pharmacology and molecular docking.Methods The chemical composition and target proteins of Xionggui Liujunzi Fromula were searched in TCMSP platform.COPD disease targets were searched in the database GeneCards using Chronic Obstructive Pulmonary Disease as a keyword,and the cross-targets of Xionggui Liujunzi Fromula target proteins and COPD disease targets were taken;then the cross-targets were used to construct a PPI network on String.Cytoscape 3.8.0 was used to construct the“Herb-Components-Targets”network and screen the core components;Cytohubba was used to screen the coretargets in the PPI network and perform bioinformatics enrichment analysis.Autodock Vina was used to perform molecular docking of the potential pharmacopoeias to the key targets.Results 154 active ingredients of Xionggui Liujunzi Fromula and 284 corresponding target proteins were obtained from the TCMSP platform;3854 COPD disease targets were obtained from the GeneCards database search,and 163 potential therapeutic targets were cross-linked with the target proteins.Ten core active ingredients were obtained by network analysis;14 core targets were obtained by Cytohubba screening;126 pathways were obtained by KEGG enrichment analysis of core targets,and 635 pathways were obtained by GO enrichment analysis.Conclusion Xionggui Liujunzi Fromula may play a role in the treatment of COPD by regulating the NOD-like receptor、TOLL-like receptor and IL^(-1)7 signaling pathway,thereby inhibiting the formation of pro-inflammatory and inflammatory factors,chemotaxis of inflammatory factors,relieving airway mucus hypersecretion,and delaying lung injury and airway obstruction.