基于网络药理学探讨清金化浊方治疗慢阻肺的作用机制

Discussion on the Mechanism of Qingjin Huazhuo Recipe in Treating Chronic Obstructive Pulmonary Disease Based on Network Pharmacology

目的 利用网络药理学方法探讨清金化浊方治疗慢阻肺的作用机制。方法 在中药系统药理学数据库和分析平台(Traditional Chinese Medicine Systems Pharmacology,TCMSP)平台检索组方君臣药物的主要化学成分及作用靶点,通过TTD、CTD、DisGeNET、GeneCards数据库获得慢性阻塞性肺疾病(Chronic Obstructive Pulmonary Disease,COPD)相关靶点,筛选药物与疾病的交集靶点及有效活性成分。利用Cytoscape3.7.2构建药物-化合物-靶点-疾病网络,利用STRING数据库构建蛋白质-蛋白质相互作用关系(Protein-Protein Interaction,PPI)网络拓扑分析图,并分析核心靶点。利用DAVID数据库进行基因功能(Gene Ontology,GO)和基于京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析,并绘制通路-靶点网络图。基于网络分析结果,纳入2020年1月-2021年1月我科收治的AECOPD患者,采用区组随机法按1:1分为对照组(西医治疗组)、研究组(清金化浊方联合西医治疗组),比较两组患者的IL-6、TNF-α水平。结果 筛选得到164个中药成分靶点,3051个COPD靶点,映射得出药物-疾病交集靶点112个。分析得出清金化浊方治疗COPD主要有槲皮素、β-谷甾醇、山奈酚、豆甾醇、木犀草素等有效活性成分,涉及IL-6、TNF、MAPK3、VEGFA、TP53、PTGS2、MAPK1、PIK3CG等关键靶点。富集于药物反应、一氧化氮生物合成过程的正调控、缺氧反应等生物过程及83条信号通路,其中TNF、HIF-1和PI3K-Akt信号通路在COPD的治疗中最为重要。临床研究显示,两组治疗7天后IL-6、TNF-α均较治疗前下降;治疗后组间比较,研究组低于对照组(P<0.05)。结论 清金化浊方主要以抗炎为核心,兼有调节氧平衡、降低气道黏液高分泌、改善气道重塑、调节免疫功能及血液高凝状态等多方面的作用,为其临床应用提供一定指导价值,亦为进一步开展后续课题研究提供科学依据。

Objective To explore the mechanism of Qingjin Huazhuo Recipe in the treatment of Chronic Obstructive Pulmonary Disease(COPD) by using network pharmacology.Methods We searched the main chemical components and targets of the prime and ministerial drugs in prescription on the TCMSP platform, and COPD-related targets were obtained through the TTD, CTD, DisGeNET, and GeneCards databases to screen the intersection targets and effective active components of drugs and diseases. Cytoscape3.7.2 was used to construct a drug-compound-target-disease network. The STRING database was used to construct a PPI network collateral topological analysis map, and core targets were analyzed. Gene function(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) based enrichment analyses were performed using the DAVID database, and pathway-target network maps were drawn. Based on the results of network analysis, patients with AECOPD admitted from January 2020 to January 2021 were included and divided into control group(western medicine treatment group) and study group(Qingjin Huazhuo Fang combined with western medicine treatment group) according to the ratio of 1:1 by block randomization. The levels of IL-6 and TNF-α were compared between the two groups.Results The screening resulted in 164 TCM component targets, 3051 COPD targets,and 112 drug-disease intersection targets mapped. It was concluded that Qingjin Huazhuo Recipe mainly had effective active components such as quercetin, β-sitosterol, kanamycin, stigmasterol, and luteolin in the treatment of COPD,involving key targets such as IL-6, TNF, MAPK3, VEGFA, TP53, PTGS2, MAPK1, and PIK3CG. It was enriched in biological processes such as drug response, positive regulation of nitric oxide biosynthesis process, hypoxia response and83 signaling pathways, of which TNF, HIF-1 and PI3K-Akt signaling pathway were the most important in the treatment of COPD. Clinical studies showed that IL-6 and TNF-α in both groups decreased after 7 days of treatment compared with those before treatment;after treatment, the study group was lower than the control group(P<0.05). Conclusion Qingjin Huazhuo Recipe mainly takes anti-inflammatory as the core, and has many functions such as regulating oxygen balance, reducing airway mucus hypersecretion, improving airway remodeling, regulating immune function and blood hypercoagulability. It provides some guiding value for its clinical application, and also provides a scientific basis for further development of subsequent topic research.