目的 基于“伏风暗瘀宿痰”小儿哮喘病机新说，采用网络药理学及实验验证的方法，探索搜风愈喘方拆方“祛宿痰方”治疗儿童哮喘的作用机制，验证中医“宿痰”病机与西医细胞外基质改变病理之间的交通性。方法 通过TCMSP数据库建立“祛宿痰方”的有效成分和靶点数据集，利用OMIM、GeneCards、DrugBank、TTD疾病数据库建立哮喘疾病靶点数据集，利用Cytoscape软件取交集并构建“祛宿痰方”与哮喘的蛋白质互作网络，筛选关键靶点蛋白。利用Metascape数据库进行基因本体（Gene ontology，GO）分析以及京都基因和基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）富集分析。复制卵蛋白（OVA）诱导的哮喘大鼠模型，对核心通路及关键靶点进行实验验证。结果 共得到“祛宿痰方”治疗哮喘的靶点98个，包括IL-13、TP53、TGF-β1、VEGF-A、MMP9等，KEGG得到与哮喘相关的通路287条（P＜0.05），包括NF-κB信号通路、PI3K-AKT信号通路、IL-17信号通路等。GO结果显示与哮喘相关生物进程包括炎症反应、细胞外基质调控、氧化应激、血管生成等。动物实验证实“祛宿痰方”可下调大鼠肺组织中p-NF-κB-P65磷酸化水平，抑制NF-κB信号通路的激活，降低IL-13、TGF-β1 mRNA表达量（P<0.05），减少哮喘大鼠肺组织中炎症细胞浸润、黏液产生，从而延缓哮喘的进程。结论 “祛宿痰方”可抑制NF-κB信号通路的激活，降低肺组织中IL-13、TGF-β1 mRNA表达量，可能通过抑制炎症反应、调控细胞外基质等途径作用于哮喘，中医“宿痰”病机与西医细胞外基质改变病理之间存在一定的的交通性。

Objective To verify the communication between the pathogenesis of traditional Chinese medicine "Su tan" and the pathological changes of extracellular matrix in western medicine. Based on the new theory of the pathogenesis of infantile asthma of "Fu Feng An Yu Su Tan", the methods of network pharmacology and experimental verification were used to explore the mechanism of "Qusutan prescription" in the treatment of childhood asthma.Methods The data sets of effective components and targets of expectorant drugs were established by TCMSP database, and the data sets of asthma disease targets were established by OMIM, GeneCards, DrugBank, TTD disease database. The protein interaction network between "Qusutan prescription" and asthma was constructed by using Cytoscape software to screen the key target proteins. Target gene ontology (GO) analysis and signal pathway (KEGG) enrichment analysis were carried out by using Metascape database. The rat model of asthma induced by ovalbumin (OVA) was replicated, and the core pathways and targets were verified by experiments.Results A total of 98 expectorant targets were obtained, including IL-13, TP53, TGF-β1, VEGF-A, MMP9 and so on. 287 pathways related to asthma were obtained by KEGG, including NF-κB signal pathway, PI3K-AKT signal pathway, IL-17 signal pathway and so on. Animal experiments showed that expectorant could down-regulate the phosphorylation level of NF-κB-p65, inhibit the activation of NF-κB signal pathway, reduce the expression of IL-13 and TGF-β1 mRNA in lung tissue, and reduce inflammatory cell infiltration and mucus production in lung tissue of asthmatic rats, thus delaying the progression of asthma.Conclusion "Qusutan prescription" can inhibit the activation of NF-κB signal pathway and reduce the expression of IL-13 and TGF-β1 mRNA in lung tissue, which may act on asthma by inhibiting inflammatory reaction and regulating extracellular matrix. There is a certain communication between the pathogenesis of traditional Chinese medicine "Su tan" and the pathology of extracellular matrix changes in western medicine.

国家自然科学基金委员会面上项目（81973903）：基于哮喘中西医病机交通性之搜风愈喘方及其拆方调控哮喘大鼠气道重塑机制的实验研究，负责人：闫永彬。