基于UHPLC-QE-MS和网络药理学探讨玉屏风散治疗慢性阻塞性肺疾病作用机制  

Exploration on the mechanism of Yupingfeng Powder on COPD patients based on UHPLC-QE-MS and network pharmacology

作　　者：刘海叶 葛美娜 王杰鹏 韩颖[2] Liu Haiye;Ge Meina;Wang Jiepeng;Han Ying(School of Basic Medical Sciences,Hebei University of Chinese Medicine,Shijiazhuang 050200,China;Department of Traditional Chinese Medicine,Third Hospital of Hebei Medical University,Shijiazhuang 050051,China)

机构地区：[1]河北中医药大学基础医学院,石家庄050200 [2]河北医科大学第三医院中医科,石家庄050051

出　　处：《国际中医中药杂志》2024年第12期1615-1621,共7页International Journal of Traditional Chinese Medicine

基　　金：河北省中医药管理局科研计划项目(2019072)。

摘　　要：目的通过超高效液相色谱-四级杆静电场轨道阱质谱(UHPLC-QE-MS)结合网络药理学和分子对接技术探讨玉屏风散治疗COPD的作用机制。方法采用UHPLC-QE-MS技术检测玉屏风散化学成分,利用ChEMB、TCMIO数据库获取其作用靶点;通过TTD、GeneCards、SymMap、DisGeNET数据库获得COPD相关靶点,取二者交集。对交集靶点进行GO功能及KEGG通路富集分析。选取匹配靶点较多的前20位化学成分,将其对应靶点与前20位KEGG通路对应靶点取并集,获得玉屏风散治疗COPD的潜在靶点,构建靶点PPI网络,筛选玉屏风散治疗COPD的关键靶点,并利用分子对接进行验证。结果正、负离子模式下,共鉴定到玉屏风散有效成分73个,排名前3位的是染料木黄酮、芹菜素、山柰酚。通过数据库获取玉屏风散有效成分作用靶点449个,COPD靶点3455个,取二者交集,获得交集靶点294个。GO功能富集分析获得生物过程2647条、细胞组分126条,分子功能289条,涉及对营养水平、细胞外刺激、氧化应激反应等。KEGG通路分析获得69条通路,涉及癌症通路、非小细胞肺癌信号通路、VEGF信号通路、T细胞受体信号通路、花生四烯酸代谢、Toll样受体信号通路等。前20位KEGG通路与匹配靶点较多的前20个化学成分共对应靶点281个,关键靶点为TP53、STAT3、c-Jun、AKT1、ESR1。分子对接结果显示,染料木黄酮、芹菜素、山柰酚与核心靶点TP53、STAT3、c-Jun结合良好。结论玉屏风散可能通过多成分、多靶点、多通路影响COPD炎症、免疫调节、氧化应激水平等,从而对COPD进展产生影响。Objective To explore the mechanism of Yupingfeng Powder on patients with chronic obstructive pulmonary disease(COPD)through UHPLC-QE-MS combined with network pharmacology and molecular docking technology.Methods UHPLC-QE-MS technology was used to detect the chemical composition of Yupingfeng Powder,and its targets were obtained using ChEMB and TCMIO databases;COPD treatment targets were obtained from TTD,GeneCards,SymMap,and DisGeNET databases,and the intersection of the two was taken.GO enrichment analysis and KEGG pathway analysis were performed on intersection targets.Top 20 metabolites with the most matching targets were selected,their corresponding targets with the top 20 KEGG pathway targets were merged,and potential targets for the treatment of COPD with Yupingfeng Powder were obtained.A target protein-target protein interaction network(PPI)was constructed,key targets of Yupingfeng Powder for the treatment of COPD were screened,and molecular docking was used for validation.Results Under positive and negative ion modes,a total of 73 active components were identified in Yupingfeng Powder.The top three ranked in terms of degree were genistein,apigenin,and kaempferol.449 targets of 73 active components and 3455 disease targets were obtained from the database.The intersection of the two was obtained,resulting in 294 common targets.A total of 69 pathways were identified through KEGG pathway analysis,involved in the pathogenesis of cancer,non-small cell lung cancer signaling pathway,VEGF signaling pathway,T cell receptor(TCR)signaling pathway,arachidonic acid metabolism,Toll like receptor signaling pathway,etc.GO enrichment analysis obtained 2647 biological processes,126 cellular components,and 289 molecular functions,involving reactions to nutritional levels,extracellular stimuli,oxidative stress,etc.The top 20 KEGG pathways and the top 20 metabolites with the most matching targets correspond to a total of 281 targets.The key targets were TP53,STAT3,c-Jun,AKT1,and ESR1.The molecular docking results showed that g

关 键 词：玉屏风散 肺疾病 慢性阻塞性 网络药理学 分子对接模拟 

分 类 号：R285[医药卫生—中药学]