基于网络药理学和生物信息学的小青龙汤治疗哮喘和慢性阻塞性肺疾病的“异病同治”机制分析

Mechanism of"treating different diseases with same method"of Xiaoqinglong Decoction in treating asthma and chronic obstructive pulmonary disease based on network pharmacology and bioinformatics

目的基于网络药理学与生物信息学研究方法,探讨小青龙汤治疗慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)和哮喘“异病同治”的疗效及其作用机制。方法通过ETCM数据库、DisGeNET数据库、GeneCards数据库、OMIM数据库搜集小青龙汤治疗COPD和哮喘的作用靶点。通过STRING 11.0分析作用靶点之间的相互关系,运用cytoNCA和MCODE插件筛选出核心作用靶点。使用ClueGO和DAVID数据库对作用靶点进行KEGG通路富集分析和GO功能分析。在GEO数据库下载COPD和哮喘的基因芯片,运用R语言sav包去批次效应后验证核心作用靶点是否差异表达,并对差异表达明显的核心靶点进行分子对接验证。结果共筛选出小青龙汤治疗COPD和哮喘的作用靶点95个,筛选出19个核心作用靶点。富集分析结果显示共涉及82条信号通路及120种生物过程、16种分子功能、21种细胞组分。GEO芯片验证显示NR3C1、HSP90AA1、TNF、CASP3、AKT1、PTGS2、TLR4、EGF、IL1B、HRAS在COPD和哮喘与健康样本之间具有明显的表达差异,绘制中药-化合物-靶点网络图后,进一步对Degree值前5的靶点进行分子对接,结果显示活性成分与关键靶点有良好的亲和力。结论小青龙汤主要通过NR3C1、HSP90AA1、TNF、CASP3、AKT1、PTGS2、TLR4、EGF、IL1B、HRAS等多靶点和TNF信号通路、Toll样受体信号通路等途径发挥对COPD与哮喘“异病同治”作用。

Objective To investigate the efficacy and the mechanism of"treating different diseases with same method"of Xiaoqinglong Decoction for chronic obstructive pulmonary disease(COPD)and asthma based on network pharmacology and bioinformatics research methods.Methods The targets of Xiaoqinglong Decoction for COPD and asthma were collected through ETCM database,DisGeNET database,GeneCards database and OMIM database.The interrelationships between the targets were analyzed by STRING11.0,and the core targets were screened using cytoNCA and MCODE plug-ins.KEGG pathway enrichment analysis and GO functional analysis were performed on the acting targets using ClueGO and DAVID databases.Gene chips for COPD and asthma were downloaded from the GEO database,and the R language sav package was applied to verify whether the core acting targets were differentially expressed after de-batching effect,and molecular docking was performed to verify the core targets with significant differential expression.Results A total of 95 action targets of Xiaoqinglong Decoction for COPD and asthma were screened,and 19 core action targets were screened.The results of enrichment analysis showed that a total of 82 signaling pathways and 120 biological processes,16 molecular functions and 21 cellular components were involved.The GEO microarray validation showed that NR3C1,HSP90AA1,TNF,CASP3,AKT1,PTGS2,TLR4,EGF,IL1B,HRAS had significant expression between COPD and asthma and healthy samples.After mapping the herbal-compound-target network,further molecular docking of the targets in the top five of Degree showed that the active ingredients had good affinity with the key targets.Conclusion Xiaoqinglong Decoction mainly exerted the effect of"treating different diseases with same method"on COPD and asthma through multiple targets such as NR3C1,HSP90AA1,TNF,CASP3,AKT1,PTGS2,TLR4,EGF,IL1B,HRAS and signaling pathways such as TNF signaling pathway and Toll-like receptor signaling pathway.