从“表型-证候-中药”关联网络探索哮喘气道重塑不同证候表型下的药物表型组学特征及机制  

Pharmacophenomics characteristics and mechanisms of traditional Chinese medicine under different symptomatic phenotypes of asthma airway remodeling based on“phenotype-syndrome-traditional Chinese medicine”association network

作　　者：王婷[1,2,3,4] 饶玲[1,2,3,4] 梁锦荣 张妙芬 黄慧婷 罗之彦 江勇[5] 詹少锋 刘琼 黄秀芳[1,2,3,4] WANG Ting;RAO Ling;LIANG Jinrong;ZHANG Miaofen;HUANG Huiting;LUO Zhiyan;JIANG Yong;ZHAN Shaofeng;LIU Qiong;HUANG Xiufang(The First Clinical Medical School,Guangzhou University of Chinese Medicine,Guangzhou 510405,China;The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405,China;Lingnan Medical Research Center of Guangzhou University of Chinese Medicine,Guangzhou 510405,China;Guangdong Clinical Research Academy of Chinese Medicine,Guangzhou 510405,China;Shenzhen Hospital of Integrated Traditional Chinese and Western Medicine,Shenzhen 518104,China)

机构地区：[1]广州中医药大学第一临床医学院,广东广州510405 [2]广州中医药大学第一附属医院,广东广州510405 [3]广州中医药大学岭南医学研究中心,广东广州510405 [4]广东省中医临床研究院,广东广州510405 [5]深圳市中西医结合医院,广东深圳518104

出　　处：《中草药》2025年第4期1292-1309,共18页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金面上项目(82204985);广东省自然科学基金面上项目(2023A1515010807,2024A1515012183);广州市科技化项目(2023A04J1854);广东省教育厅项目青年创新人才项目(2022KQNCX013);深圳市“医疗卫生三名工程”建设项目(SZZYSM202206013);广东省重点科室(中西医协同科室)建设项目;国家中医优势专科建设项目(广州中医药大学第一附属医院肺病科);广州中医药大学第一附属医院青优人才项目;广州中医药大学青年拔尖人才(团队)培育“揭榜挂帅”项目;中华中医药青年人才托举工程项目(2024-QNRC2-B38);“广东特支计划”省卫生健康委(卫生健康人才)项目(0720240224);深圳宝安区中医药临床研究专项(2023ZYYLCZX-9,2023ZYYLCZX-11);广东省中医药局科研项目(20251334);深圳市科技创新局基础研究面上项目(JCYJ20240813114911016);深圳市宝安区深圳市宝安区医疗卫生科研项目(2023JD124,2023JD107,2023JD105,2023JD110,2024JD289,2024JD293,2024JD316);深圳市宝安区医学会医疗卫生科研项目(BAYXH2024011);深圳市中西医结合医院院内课题(YJ-2023-106,YJ-2023-104,YJ-2023-115)。

摘　　要：目的从“表型-证候-中药”关联网络,探索哮喘气道重塑不同证候表型下的药物表型组学特征及机制。方法收集中医药干预哮喘气道重塑的临床研究文献(检索范围为建库至2024年3月24日),提取中医药信息要素及气道重塑相关指标,进行证候表型分类,运用RStudio执行描述性统计,并通过Apriori算法、点式互信息法对各证候表型链接的中药及中药链接的哮喘气道重塑指标进行关联规则探索及hclust函数挖掘核心中药组方。利用HERB、GeneCards数据库联合鉴定核心中药组方治疗哮喘气道重塑的靶标谱。马尔可夫聚类算法(Markov cluster algorithm,MCL)挖掘关键功能基因簇,筛选关键靶点,并借助人气道上皮、鼻拭子、痰液样本数据表征关键靶点对哮喘气道重塑的贡献价值,最后采用过表征分析各关键功能基因簇的通路及生物功能。结果纳入76篇文献,哮喘分为冷哮、风哮、热哮、虚哮、瘀哮5个证候表型,筛选得到139味中药,涉及转化生长因子-β1(transforming growth factor-β1,TGF-β1)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、基质金属蛋白酶-9(matrix metalloproteinases-9,MMP-9)等重塑指标。中药表型特征方面,冷哮以散寒解表化痰药为主(组方为射干、干姜、细辛、桂枝),风哮以祛风涤痰解痉药为主(组方为莱菔子、紫苏子、僵蚕、橘红、防风、地龙、荆芥、半夏、麻黄、陈皮、茯苓、五味子),热哮以清肺泄热化痰药为主(组方为桑白皮、蝉蜕、厚朴、苦杏仁、款冬花、黄芩、浙贝母、白果、白前),虚哮以益气养阴固本功效为主(组方为补骨脂、甘草、麦冬、山药、党参、黄芪、白术),瘀哮以活血祛瘀化痰药为主(组方为当归、熟地黄、牡丹皮、丹参、大枣、桃仁、红参、川芎、白芍、北沙参)。中药与重塑指标关联方面,甘草、苦杏仁、麻黄、半夏、陈皮与TGF-β1、MMP-9、气道壁面积(wall area,WObjective To explore the pharmacophenomics characteristics and mechanisms of traditional Chinese medicine(TCM)under different symptomatic phenotypes of asthma airway remodeling based on“phenotype-syndrome-Chinese medicine”association network.Methods Collect the clinical research literature of TCM intervention on asthma airway remodeling(Scope of search:library build to 24 March 2024),extract TCM information elements and asthma airway remodeling related indicators and classify the syndrome phenotype.Descriptive statistics were performed by RStudio,and the association rules of TCM and airway remodeling indicators of TCM linked by syndrome phenotype were explored by Apriori algorithm and point mutual information method,and the core TCM prescription was mined by hclust function.HERB and the GeneCards database were used to identify the target spectrum of the core TCM prescription for airway remodeling.Markov cluster algorithm(MCL)was used to mine the key functional gene clusters and screen key targets.Human airway epithelial,nasal swab and sputum sample data were used to characterise the contribution of key targets to airway remodeling.Finally,the pathways and biological functions of the key functional gene clusters were analysed by over-representation analysis(ORA).Results A total of 76 literatures were included,which were divided into five syndrome phenotypes:cold asthma,wind asthma,heat asthma,deficiency asthma and blood stasis asthma,and 139 TCMs involving remodeling indicators such as transforming growth factor-β1(TGF-β1),tumor necrosis factor-α(TNF-α),matrix metalloproteinases-9(MMP-9),etc.In terms of the phenotypic characteristics of TCM,cold asthma was mainly effective in dispelling cold,diaphoresis relieving superficies and resolving phlegm[Shegan(Belamcandae Rhizoma),Ganjiang(Zingiberis Rhizoma),Xixin(Asari Radix et Rhizoma),Guizhi(Cinnamomi Ramulus)],wind asthma was mainly in dispelling wind,purging phlegm and spasmolysis[Laifuzi(Raphani Semen),Zisuzi(Perillae Fructus),Jiangcan(Bombyx Batryticatus),

关 键 词：哮喘 气道重塑 中医药表型组学 证候表型组学 中药药物表型组学 转化生长因子-β1 肿瘤坏死因子-α 基质金属蛋白酶-9 甘草 苦杏仁 麻黄 半夏 陈皮 

分 类 号：Q811.4[生物学—生物工程] R285[医药卫生—中药学]