基于转录组学与网络药理学分析射麻止喘液治疗嗜酸性粒细胞型哮喘的分子机制  

Integrative Transcriptomics and Network Pharmacology to Analyze the Molecular Mechanism of Shema Zhichuan Liquid in Treating Eosinophilic Asthma

作　　者：宋栋 李慧聪 高雪歌 谢燕小 孟星汝 周谨希 蒋紫云[1,4] 连乐燊 SONG Dong;LI Huicong;GAO Xuege;XIE Yanxiao;MENG Xingru;ZHOU Jinxi;JIANG Ziyun;LIAN Leshen(Dongguan Hospital Affiliated to Guangzhou University of Chinese Medicine,Dongguan 523000 Guangdong,China;Graduate School of Guangzhou University of Chinese Medicine,Guangzhou 510006 Guangdong,China;Graduate School of Southern Medical University,Guangzhou 510515 Guangdong,China;The Third Clinical Medical School of Guangzhou University of Chinese Medicine,Guangzhou 510370 Guangdong,China;The First Clinical Medical School of Guangzhou University of Chinese Medicine,Guangzhou 510405 Guangdong,China)

机构地区：[1]广州中医药大学东莞医院,广东东莞523000 [2]广州中医药大学研究生院,广东广州510006 [3]南方医科大学研究生院,广东广州510515 [4]广州中医药大学第三临床医学院,广东广州510370 [5]广州中医药大学第一临床医学院,广东广州510405

出　　处：《中药新药与临床药理》2024年第12期1886-1894,共9页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：广东省基础与应用基础研究基金项目(2021A1515010146)。

摘　　要：目的基于转录组学与网络药理学分析射麻止喘液治疗嗜酸性粒细胞型哮喘(Eosinophilic asthma,EA)的分子机制。方法(1)收集10例急性发作期(轻、中度)EA患者和10例健康志愿者的外周血样本,采用转录组测序技术对两组样本进行建库测序,筛选出EA的差异表达基因(DEGs)。(2)利用TCMSP平台、文献检索及Swiss ADME、Swiss Target Prediction数据库筛选射麻止喘液的活性成分及其作用靶点。对射麻止喘液活性成分的作用靶点与EA的差异表达基因取交集,得到射麻止喘液治疗EA的关键靶点。构建关键靶点的蛋白互作(PPI)网络,通过节点度值筛选核心靶点。构建“中药-活性成分-关键靶点”网络,并分析筛选出射麻止喘液治疗EA的关键活性成分。使用Metascape平台对关键靶点进行GO功能及KEGG通路富集分析。对核心靶点与关键活性成分进行分子对接验证。结果筛选得到2109个差异表达基因,其中上调基因922个,下调基因1187个。共获得102种射麻止喘液的活性成分及826个作用靶点,取交集后得到74个射麻止喘液治疗EA的关键靶点。PPI网络分析得到IFNG、PTGS2、MAPK3、CCL2、IL10和CXCL8等核心靶点。“中药-活性成分-关键靶点”网络分析得到槲皮素、木犀草素、山柰酚、β-谷甾醇、豆甾醇等关键活性成分。关键靶点主要涉及炎症反应、趋化作用、细胞对细胞因子刺激的反应等生物过程,以及PI3K-Akt、MAPK、TLRs(Toll样受体)、NF-κB及TNF等信号通路。β-谷甾醇、豆甾醇与6个核心靶点,MAPK3、PTGS2、CXCL8与5个关键活性成分均具有较强的结合能力。结论射麻止喘液对EA的治疗作用可能是通过β-谷甾醇、豆甾醇等关键活性成分,作用于MAPK3、CXCL8、PTGS2等核心靶点,调控PI3K-Akt、MAPK、NF-κB等信号通路实现的。Objective To investigate the molecular mechanism of Shema Zhichuan Liquid in the treatment of eosinophilic asthma(EA)based on transcriptomics and network pharmacology.Methods(1)Peripheral blood samples were collected from 10 patients with acute exacerbation of EA(mild to moderate)and 10 healthy control volunteers.Transcriptome sequencing was performed on both groups to construct database for sequencing and identify differentially expressed genes(DEGs)associated with EA.(2)Active components and their targets in Shema Zhichuan Liquid were identified through TCMSP,literature searches,Swiss ADME and Swiss Target Prediction databases.The intersection of DEGs of EA with targets of active components in Shema Zhichuan Liquid yielded key targets for EA treatment.A protein-protein interaction(PPI)network of these key targets was constructed.The core targets were screened according to node-degree values.“Chinese medicine-active ingredients-key targets”network was built to analyze and screen the key active ingredients of Shema Zhichuan Liquid in treating EA.The Metascape platform was used to conduct GO function and KEGG signaling pathway enrichment analysis of key targets.Finally,the binding capability between the core targets and key active components was verified through molecular docking.Results A total of 2109 DEGs,including 922 upregulated genes and 1187 downregulated genes were screened.A total of 102 active ingredients and 826 targets of Shema Zhichuan Liquid were identified.After taking the intersection,74 key targets of Shema Zhichuan Liquid in the treatment of EA were obtained.PPI analysis identified IFNG,PTGS2,MAPK3,CCL2,IL10 and CXCL8 as core targets.“Chinese medicine-active ingredients-key targets”network analysis highlighted quercetin,kaempferol,luteolin,β-sitosterol and stigmasterol as key active components.The key targets were primarily involved in biological processes including inflammatory response,chemotaxis,and cellular response to cytokines stimulus,and the signaling pathways such as PI3K-Akt,MA

关 键 词：嗜酸性粒细胞型哮喘 射麻止喘液 转录组学 网络药理学 分子对接 差异表达基因 

分 类 号：R285.5[医药卫生—中药学] R857.3[医药卫生—中医学]