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，WA）连接密切。不同证候表型中药关键靶点分别为冷哮-C-C基序趋化因子受体2（C-C motif chemokine receptor 2，CCR2）、风哮-白细胞介素17A（interleukin 17A，IL17A）、热哮-连环蛋白β1（catenin beta 1，CTNNB1）、虚哮集落刺激因子2（colony stimulating factor 2，CSF2）及瘀哮-骨形态发生蛋白2（bone morphogenetic protein 2，BMP2），气道上皮中CTNNB1、鼻拭子中CCR2、痰液中CCR2对哮喘气道重塑贡献最大。过表征分析提示，冷哮组方主要发挥抑制内质网应激和维持细胞稳态药理作用，风哮组方主要发挥调节钙通道和缓解平滑肌痉挛药理作用，热哮组方主要发挥调节免疫和抗炎药理作用，虚哮组方主要发挥抑制增殖侵袭和调节免疫应答药理作用，瘀哮组方主要发挥缓解气道纤维化药理作用。结论 通过中医药表型组学系统分析，哮喘气道重塑不同证候表型的中药药物表型各有特征，发挥的药理机制主要涉及抑制内质网应激、抗炎、调节免疫、抗增殖和抗纤维化等方面。

Objective 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), Juhong (Citri Exocarpium Rubrum), Fangfeng (Saposhnikoviae Radix), Dilong (Pheretima), Jingjie (Schizonepetae Herba), Banxia (Pinelliae Rhizoma), Mahuang (Ephedrae Herba), Chenpi (Citri Reticulatae Pericarpium), Fuling (Poria), Wuweizi (Schisandrae Chinensis Fructus)], heat asthma was mainly in clearing lung heat and resolving phlegm [Sangbaipi (Mori Cortex), Chantui (Cicadae Periostracum), Houpo (Magnoliae Officinalis Cortex), Kuxingren (Armeniacae Semen Amarum), Kuandonghua (Farfarae Flos), Huangqin (Scutellariae Radix), Zhebeimu (Fritillariae Thunbergii Bulbus), Baiguo (Ginkgo Semen), Baiqian (Cynanchi Stauntonii Rhizoma et Radix)], deficiency asthma was mainly 摩?爠整杯畮汩慦瑹楩湮杧?椼浩派畱湩攼?物放猬瀠潮湯獵敲??慨湩摮?戠汹潩潮搠?獮瑤愠獣楯獮?慯獬瑩桤浡慴?灮牧攠獴捨物楳瀠瑥楦潦湥?浴愠楛湂汵祧?灺汨慩礠攨搼?愾?灳桯慲牡浬慥捡潥氠潆杲極捣慴汵?爼漯汩放?椬渠?牡敮汣楡敯瘠椨渼杩￣慇楬特督慹祲?晨楩扺牡潥猠楒獡???戼??漾渠捥汴甠猼楩漾湒??扺??呡格爯潩甾朩栬?瑍桡敩?獯祮獧琠攨洼慩琾楏捰?慩湯慰汯祧獯楮獩?漠晒?瑤桩數?瀯桩愾爩洬愠捓潨灡桮敹湡潯洠椨挼獩￣潄晩?味????瑡桥攠?灨桩敺湯潭瑡礼瀯敩猾?漬映?呡???晨潥牮?愨椼物眾慃祯?牯敮浯潰摳敩汳椠湒条?潩晸?愯獩琾栩洬愠?桵慡癮敧?摩椠昨昼敩爾敁湳瑴?捡桧慡牬慩挠瑒敡牤楩獸琼椯捩猾??愠湂摡?瑺桨敵?瀨格慩爾流慴捲潡汣潴杹楬捯慤汩?洠敍捡档慲湯楣獥浰獨?睬敡牥攠?浨慩楺湯汭祡?爯敩氾愩瑝攬搠?瑮潤?楢湬桯楯扤椠瑳楴潡湳?潳映?敳湴摨潭灡氠慷獡浳椠捭?物敮瑬楹挠畩汮甠浰?獯瑭牯整獩獮??慢湬瑯楯?椠湣晩汲慣浵浬慡瑴楩潯湮??牲敥杭畯汶慩瑮楧漠湢?潯景?椠浳浴畡湳楩瑳礠??慤渠瑲楥?灯牬潶汩楮晧攠牰慨瑬楥潧湭?慛湄摡?慧湧瑵楩?昨椼扩爾潁獮楧獥?icae Sinensis Radix), Shudihuang (Rehmanniae Radix Praeparata), Mudanpi (Moutan Cortex), Danshen (Salviae Miltiorrhizae Radix et Rhizoma), Dazao (Jujubae Fructus), Taoren (Persicae Semen), Hongshen (Persicae Semen), Chuanxiong (Chuanxiong Rhizoma), Baishao (Paeoniae Radix Alba), Beishashen (Glehniae Radix)]. In terms of correlation between TCM and remodeling indicators, Glycyrrhizae Radix et Rhizoma, Armeniacae Semen Amarum, Ephedrae Herba, Pinelliae Rhizoma and Citri Reticulatae Pericarpium were closely linked to TGF-β1, MMP-9 and wall area (WA). Key targets of TCM for different syndrome phenotypes were cold asthma-C-C motif chemokine receptor 2 (CCR2), wind asthma-interleukin 17A (IL17A), heat asthma-catenin beta 1 (CTNNB1), deficiency asthma-colony stimulating factor 2 (CSF2) and blood stasis asthma-bone morphogenetic protein 2 (BMP2), with airway epithelial CTNNB1, nasal swab CCR2, and sputum CCR2 contributing the most to airway remodeling. ORA suggested that cold asthma prescription mainly played a pharmacological role in inhibiting endoplasmic reticulum stress and maintaining cell stability, wind asthma prescription mainly played a pharmacological role in regulating calcium channels and relieving smooth muscle spasm, heat asthma prescription mainly played a pharmacological role in regulating immunity and anti-inflammation, deficiency asthma prescription mainly played a pharmacological role in inhibiting proliferation and invasion an

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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）