文献类型：期刊文献

中文题名：基于网络药理学和分子对接研究小青龙汤治疗慢性阻塞性肺疾病的作用机制

英文题名：A study on the mechanism of the Xiaoqinglong decoction on chronic obstructive pulmonary disease based on network pharmacology and molecular docking

作者：王亚锋[1];夏晓黎[2];马艳萍[1];张宁[1];魏才杰[1]

第一作者：王亚锋

机构：[1]甘肃中医药大学,甘肃兰州730000;[2]甘肃中医药大学附属医院,甘肃兰州730000

第一机构：甘肃中医药大学

年份：2021

卷号：13

期号：22

起止页码：1

中文期刊名：中医临床研究

外文期刊名：Clinical Journal Of Chinese Medicine

基金：甘肃省中医药管理局科研项目:平喘贴联合无创正压辅助通气在老年慢阻肺肺康复中的疗效观察(GZK-2019-33)。

语种：中文

中文关键词：网络药理学;小青龙汤;分子对接;慢性阻塞性肺疾病

外文关键词：Network pharmacology;The Xiaoqinglong decoction;Molecular-docking;Chronic obstructive pulmonary disease

摘要：目的:运用网络药理学方法构建药物活性成分-疾病-靶点关系网络,通过核心靶点与主要活性成分分子对接,探究小青龙汤治疗慢性阻塞性肺疾病(Chronic Obstructive Pulmonary Disease,COPD)的作用机制。方法:从中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacolgy Database and Analysis Platform,TCMSP)检索筛选小青龙汤活性成分及其对应靶点,通过Unipot数据库检索人类基因对其靶点简化注释,然后与GeneCards、OMIM、PharmGkb、TTD、DrugBank数据库获取的疾病靶点相映射取交集;将药物活性成分及交集靶点导入Cytoscape 3.8.0软件,构建药物活性成分-疾病-靶点关系网络;运用String平台进行蛋白互作网络分析,再使用Cytoscape 3.8.0软件筛选出14个关键基因,运用R 4.0.4软件对关键靶点进行基因本体论(Gene Ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)通路富集分析并作关键靶点-成分网络示图,根据关键靶点-成分中Degree值分别筛选出前5个核心靶点和活性成分,最后运用AutoDock软件进行分子对接。结果:小青龙汤中筛选出有效成分169个,关键有效成分5个,分别是槲皮素、木犀草素、甘草酮、山奈酚、柚皮素;交集靶点221个,关键靶点14个(分别是STAT3、JUN、TP53、TNF、AKT1、RELA、MAPK1、MAPK3、MYC、CDKN1A、CCND1、MAPK14、RB1、CXCL8);GO分析得出1 444条生物学过程(Biological Process,BP),43个分子功能(Molecular Function,MF),44个细胞组分(Cellular Component,CC);KEGG分析得出与COPD关系密切的Toll样受体信号通路、白细胞介素-17(Interleukin-17,IL-17)信号通路、T细胞受体等富集信号通路146条;分子对接结果显示所有核心靶点与成分都具有一定的结合活性,且大部分具有较好的结合活性。结论:小青龙汤在干预COPD中体现了多成分、多靶点、多通路特征,该结果可为进一步深化小青龙汤治疗COPD的机制的研究提供思路。
Objective:To explore the mechanism of the Xiaoqinglong decoction(小青龙汤) on COPD by using network pharmacology method to construct drug active component disease target relationship network and docking core target with main active component molecules.Methods:The active ingredients and their corresponding targets of the Xiaoqinglong decoction were screened from TCMSP database,and the human genes were searched through Unipot database to simplify the annotation of its targets,then the cross sets were mapped with the disease targets obtained from GeneCards,OMIM,PharmGkb,TTD and Drugbank,and the drug active ingredients and their cross targets were introduced into Cytoscape 3.8.0 software to construct the drug active ingredient disease target relationship network.String platform was used to analyze protein interaction network,and then 14 key genes were screened by Cytoscape 3.8.0 software;GO and KEGG pathway enrichment analysis for the key targets was executed by R 4.0.4 software,and the key target component network diagram was made.According to the degree value of the key target component,the top five core targets and active components were selected respectively,and then the molecular docking was carried out by AutoDock software.Results:169 effective components were selected from the Xiaoqinglong decoction,5 key active components were quercetin,luteolin,glycyrrhizin,kaempferol and naringenin;there were 221 intersection targets and 14 key targets(including STAT3,JUN,TP53,TNF,AKT1,RELA,MAPK1,MAPK3,MYC,CDKN1 A,CCND1,MAPK14,RB1,CXCL8).GO analysis showed 1 444 biological processes,43 molecular functions and 44 cellular components;KEGG analysis showed 146 enriched signaling pathways closely related to COPD,such as Toll like receptor signaling pathway,IL-17 signaling pathway and T cell receptor,molecular docking results showed that all core targets and components had certain binding activity,and most of them had good binding activity.Conclusion:The Xiaoqinglong decoction has the characteristics of multi-component,multi-target and multi-channel in the intervention of COPD,which can provide ideas for further deepening the mechanism research of the Xiaoqinglong decoction on COPD.