目的 运用GEO芯片、网络药理学及分子对接技术探究炙甘草汤治疗肺纤维化的作用靶点及其潜在机制。方法 通过中药系统药理学数据库与分析平台（TCMSP）、BATMAN-TCM、ETCM数据库获取炙甘草汤的化学成分靶点并利用Uniprot校正靶点；通过GEO数据库筛选以及GeneCards、OMIM、TTD、disgenet数据库检索获取肺纤维化疾病靶点；完成药物成分靶点与疾病靶点的交集分析，借助Cytoscape软件结合STRING数据库，建立“药物-疾病-化合物-靶点”关联网络，进一步进行蛋白质-蛋白质相互作用（PPI）网络构建与拓扑分析。将筛选出的共有靶点导入Metascape数据库，进行基因本体（GO）和京都基因与基因组百科全书（KEGG）富集分析，以筛选关键信号通路。最后，通过分子对接方法验证网络药理学的预测结果，以确保其可靠性。结果 共获得171种炙甘草汤活性成分，与肺纤维化相关的交集靶点有417个。经过PPI网络的筛选，确定了19个核心靶点，其中排名前5的是磷酸甘油醛脱氢酶（GAPDH）、蛋白激酶B（Akt1）、肿瘤坏死因子（TNF）、白蛋白（ALB）和白细胞介素6（IL6）。GO富集分析结果显示，炙甘草汤主要调节细胞对外界刺激的反应、氧化应激以及基因转录等关键生物学过程。KEGG通路富集分析揭示了包括癌症信号通路、脂质代谢与动脉粥样硬化、TNF、IL-17、磷脂酰肌醇-3-激酶/蛋白激酶B（PI3K/Akt）、丝裂原活化蛋白激酶（MAPK）、AGE-RAGE和低氧诱导因子-1（HIF-1）在内的多条信号通路。分子对接结果验证了炙甘草汤的前5种活性成分与5个关键蛋白的结合能均不高于-25 kJ·mol^-1，表明结合稳定且有显著潜力。结论 炙甘草汤中的多种活性成分可以通过多靶点、多信号通路针对肺纤维化发挥治疗作用，为后续实验和临床研究提供参考依据。

Objective To investigate the key therapeutic targets and potential mechanisms of action of Zhigancao Decoction in the treatment of pulmonary fibrosis by using GEO chip, network pharmacology and molecular docking techniques.Methods After performing an intersection analysis between the drug component targets and the disease targets, the Cytoscape software, in conjunction with the STRING database, was employed to construct a "disease-drug-compound-target" association network. Further, a proteinprotein interaction (PPI) network was constructed, and topological analysis was conducted. The screened common targets were inputted into the metascape database for GO and KEGG enrichment analysis, and the key signaling pathways were screened out. Finally, the network pharmacology results were validated using molecular docking technology.Results A total of 171 active ingredients were obtained. There were 417 targets intersecting with pulmonary fibrosis, and through PPI screening, 19 core targets were finally obtained, and the top 5 were GAPDH, Akt1, TNF, ALB, and IL6. The results of GO enrichment analysis showed that Zhigancao Decoction was mainly involved in the regulation of cellular responses to external stimuli, oxidative stress, transcriptional regulation, and other biological processes. KEGG pathway enrichment analysis revealed several signaling pathways, including cancer signaling pathways, lipid metabolism and atherosclerosis, TNF signaling pathway, IL-17 signaling pathway, PI3K/Akt signaling pathway, MAPK signaling pathway, AGE-RAGE signaling pathway, and HIF-1 signaling pathway. Furthermore, molecular docking results demonstrated that the binding energies of top five active components of Zhigancao Decoction with the five major targets were all below -25 kJ·mol^-1, indicating stable binding and significant potential for therapeutic application.Conclusion The various active components in Zhigancao Decoction can exert therapeutic effects on pulmonary fibrosis through multiple targets and signaling pathways, providing a reference for subsequent experiments and clinical research.

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国家自然科学基金青年项目（82104624）；江苏省自然科学基金青年项目（BK20240731）；国家中医药管理局高水平中医药重点学科建设项目资助（国中医药人教函[2023]85号）；大学生创新创业训练国家级项目（202410315058Z）