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 2 109 个差异表达基因，其中上调基因 922 个，下调基因 1 187 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 2 109 DEGs，including 922 upregulated genes and 1 187 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，MAPK，Toll-like receptor，NF- κB and TNF. Molecular docking indicated β -sitosterol and stigmasterol have strong binding affinities for six core targets， while MAPK3，PTGS2 and CXCL8 showed good binding ability with five key active ingredients. Conclusion The therapeutic effects of Shema Zhichuan Liquid on EA may be mediated through key active components，such as β-sitosterol and stigmasterol，which acted on core targets （MAPK3，CXCL8 and PTGS2） and regulated signaling pathways （PI3K-Akt，MAPK，and NF-κB）.

R285.5；R857.3

广东省基础与应用基础研究基金项目（2021A1515010146）