目的 基于数据挖掘、网络药理学及分子对接，分析国家中药复方专利治疗支气管哮喘的用药规律以及核心药物的药效机制。方法 在中国专利公布公告网检索，提取治疗支气管哮喘及其常见临床表型的中药复方，借助古今医案云平台（V2.3.5）规范药物名称，对中药进行用药频次、性味归经、关联规则、系统聚类和复杂网络分析，并筛选出核心处方。通过各中药药理数据库、分析平台及文献查阅获取核心处方药物的活性成分并预测其作用靶点；通过各疾病数据库收集支气管哮喘靶点，获取核心处方药物成分治疗支气管哮喘的潜在靶点；通过STRING 12.0数据库分析蛋白质-蛋白质相互作用（PPI）网络，借助Cytoscape 3.10.3软件构建药物-成分-靶点网络，对潜在靶点进行基因本体（GO）注释及京都基因与基因组百科全书（KEGG）通路富集分析以探究中药复方专利核心处方治疗支气管哮喘的可能药效机制，并应用AutoDock Vina 1.1.2软件对关键成分与核心靶点进行分子对接。结果 共收集470首中药复方，涉及中药900味，其中有27味中药使用频次≥50，占总频次的39.65%。性味归经分析显示，温、平、寒为最常见中药药性，辛、甘、苦为最常见药味，肺、脾、胃、心、肝为最常见归经。关联规则分析表明，有15组药对为中药复方专利治疗支气管哮喘常用药物组合，包括地龙与麻黄、紫苏子与苦杏仁、苦杏仁与麻黄等。系统聚类显示，中药专利复方高频药物可分为射干麻黄汤类方、清气化痰丸类方、麻黄-苦杏仁、甘草4类。复杂网络分析显示，治疗支气管哮喘的核心药物包括麻黄、苦杏仁、甘草、半夏、桔梗、五味子。网络药理学分析结果显示，中药专利复方核心处方“麻黄-苦杏仁-半夏-桔梗-五味子-紫苏子-地龙-甘草”的主要活性成分可能包括槲皮素、花生四烯酸、二十碳五烯酸、木犀草素、山柰酚、黄芩素、柚皮素等，这些成分可能作用于热休克蛋白90α家族A类成员1(HSP90AA1)、G1/S-特异性周期蛋白-D1(CCND1)、雌激素受体1(ESR1)、丝裂原活化蛋白激酶1(MAPK1)等关键靶点，并通过调控肿瘤坏死因子（TNF）、白细胞介素-17(IL-17)、C型凝集素受体（CLRs）等多条信号通路发挥作用。分子对接验证结果提示，除花生四烯酸、二十碳五烯酸外的其他核心成分与关键靶点均有良好的结合能力，关键靶点肿瘤蛋白p53(TP53)与所有核心成分均结合良好。结论 治疗支气管哮喘的中药复方专利核心处方药物包括麻黄、苦杏仁、半夏、桔梗、五味子、紫苏子、地龙、甘草，其作用机制可能主要与改善气道炎症、调节免疫相关。

Objective Based on data mining and network pharmacology methods, this study aims to analyze the medication patterns and pharmacodynamic mechanisms of core drugs in Chinese medicine patent formulas for the treatment of bronchial asthma. Methods Chinese patent formulas for treating bronchial asthma and its common clinical phenotypes were obtained through the China Patent Publication Database. The names of the herbs were standardized, and drug frequency, properties, meridian tropism, association rules, and complex network analyses were conducted using the Gujin Medical Cloud Platform（V2.3.5）. Core formulas were then screened. Active ingredients and potential targets of the core drugs were predicted using relevant pharmacology databases, literature, and analysis platforms. Disease databases were consulted to gather asthma-related targets. Protein-protein interaction（PPI） and key target networks were analyzed using STRING 12.0, and a core drug-component-target network was constructed with Cytoscape 3.10.3. Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） enrichment analyses were performed to explore the molecular mechanisms of the core formulas for asthma treatment. Results A total of 470 Chinese medicine formulas were collected, involving 900 herbs. Among them, 27 herbs appeared more than 50 times, accounting for 39.65% of the total frequency. The main properties of these herbs were warm, neutral, and cold; the dominant tastes were pungent, sweet, and bitter; and the primary meridians were lung, spleen, stomach, heart, and liver. Association rules revealed 15 common drug combinations, such as Pheretima and Ephedrae Herba, Perillae Fructus and Armeniacae Semen Amarum, and Armeniacae Semen Amarum and Ephedrae Herba. Systematic clustering analysis reveals that high-frequency herbs in patented Chinese herbal compound prescriptions can be categorized into four classes: Shegan Mahuang Decoction-type formulas, Qingqi Huatan Pilltype formulas, Ephedrae Herba-Armeniacae Semen Amarum, and Glycyrrhizae Radix et Rhizoma. Complex network analysis identified Ephedrae Herba, Armeniacae Semen Amarum, Glycyrrhizae Radix et Rhizoma, Pinelliae Rhizoma, Platycodonis Radix, and Schisandrae Chinensis Fructus as the core drugs. Network pharmacology analysis showed that the main active ingredients of the core formula “Ephedrae Herba-Armeniacae Semen Amarum-Pinelliae Rhizoma-Platycodonis Radix-Schisandrae Chinensis Fructus-Perillae Fructus-Pheretima-Glycyrrhizae Radix et Rhizoma” might include quercetin, arachidonic acid, eicosapentaenoic acid, luteolin, kaempferol, baicalein, naringenin, etc. These components may act on key targets such as HSP90 AA1, CCND1, ESR1, MAPK1, and regulate multiple signaling pathways, including TNF, IL-17, and C-type lectin receptors. The molecular docking results indicate that, except for arachidonic acid and eicosapentaenoic acid, all other core components exhibit strong binding affinity with the key targets. Notably, the key target TP53 demonstrates stable binding interactions with all core components. Conclusion The core formula for treating bronchial asthma includes Ephedrae Herba, Armeniacae Semen Amarum, Glycyrrhizae Radix et Rhizoma, Pinelliae Rhizoma, Platycodonis Radix, Schisandrae Chinensis Fructus, Perillae Fructus, Pheretima. Its mechanism of action is likely related to improving airway inflammation and immune regulation.

R285.5

国家自然科学基金面上项目（82074390）