目的 基于网络药理学方法和斑马鱼模型探讨瓜蒌薤白半夏汤干预慢性阻塞性肺疾病（chronic obstructive pulmoriary disease，COPD）的潜在作用机制。方法 运用中药系统药理学数据库与分析平台（TCMSP）、中医药百科全书数据库（ETCM）、中医药综合数据库（TCMID）以及国内外相关文献检索瓜蒌薤白半夏汤的主要活性成分，通过TCMSP和SwissTargetPrediction数据库预测靶点；通过GeneCards数据库、在线人类孟德尔遗传数据库（OMIM）和TCMSP数据库获取COPD相关靶点，并采用交集法筛选出与瓜蒌薤白半夏汤活性成分作用的共同靶点。运用Cytoscape 3.7.1软件构建“中药-活性成分-靶点”网络，通过String数据库构建蛋白质-蛋白质相互作用（protein-protein interaction，PPI）网络；通过DAVID数据库对共有基因进行基因本体（gene ontology，GO）功能富集分析及京都基因与基因组百科全书（Kyoto encyclopedia of genes and genomes，KEGG）通路富集分析；借助斑马鱼炎症模型对筛选的靶点进行实验验证。结果 瓜蒌薤白半夏汤共筛选出成分955个，潜在活性成分106个，核心活性成分如芹菜素、茴香酸、美迪紫檀素、金圣草黄素、香叶木素等74个，对应靶点1134个；PPI网络分析获得瓜蒌薤白半夏汤干预COPD的关键作用靶点408个，包括碳酸酐酶9（carbonic anhydrase 9，CA9）、前列腺素内过氧化物合酶1（prostaglandin-endoperoxide synthase 1，PTGS1）、胰岛素（insulin，INS）、白细胞介素-6（interleukin-6，IL-6）、丝氨酸/苏氨酸蛋白激酶1（serine/threonine protein kinase 1，AKT1）、肿瘤坏死因子（tumor necrosis factor，TNF）、丝裂原活化蛋白激酶1（mitogen-activated protein kinase 1，MAPK1）、MAPK3、血管内皮生长因子A（vascular endothelial growth factor A，VEGFA）、表皮生长因子受体（epidermal growth factor receptor，EGFR）等；GO功能及KEGG通路富集分析得出与瓜蒌半夏薤白汤干预COPD作用相关的生物过程1096个，如炎症反应、细胞溶质、酶结合等；相关信号通路125条，如癌症通路、TNF信号通路、前列腺癌、缺氧诱导因子1信号通路、神经活性配体-受体相互作用等。斑马鱼炎症模型实验结果显示，瓜蒌薤白半夏汤显著降低IL-6、B淋巴细胞2（B-cell lymphoma 2，BCL2）和EGFR mRNA表达水平（P<0.05），降低半胱氨酸蛋白酶8（Caspases 8，CASP8）mRNA表达水平。结论 瓜蒌薤白半夏汤可能通过作用于EGFR、IL-6、BCL2、CASP8等靶点，调节多条信号通路，从而发挥对COPD的治疗作用。

Objective To explore the potential mechanism of Gualou Xiebai Banxia Decoction (瓜蒌薤白半夏汤) on intervention of chronic obstructive pulmoriary disease (COPD) based on network pharmacology method and zebrafish model. Methods The main active ingredients of Gualou Xiebai Banxia Decoction were searched using TCM System Pharmacology Database and Analysis Platform (TCMSP), TCM Encyclopedia (ETCM), TCM Comprehensive Database (TCMID), and related literature at home and abroad, targets were predicted through TCMSP and SwissTargetPrediction database; COPD-related targets were obtained through GeneCards database, online human Mendelian Inheritance Database (OMIM) and TCMSP database, the common target interacts with active ingredients of Gualou Xiebai Banxia Decoction were screened out by intersection method. "Traditional Chinese medicine-active ingredients-targets" network was construct by Cytoscape 3.7.1 software, protein-protein interaction (PPI) network was construct by String database, shared genes were performed gene ontology (GO) functional enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis by DAVID database; The screened targets were verified by zebrafish inflammation model. Results A total of 955 ingredients were screened for Gualou Xiebai Banxia Decoction, 106 potential active ingredients, and 74 core active ingredients such as apigenin, anisic acid, medi pterostil, chrysophyllin, geraniol, etc., corresponding to 1134 targets; PPI network analysis obtained 408 key targets for Gualou Xiebai Banxia Decoction to interfere with COPD, including carbonic anhydrase 9 (CA9), prostaglandin-endoperoxide synthase 1 (PTGS1), insulin (INS), interleukin-6 (IL-6), serine/threonine protein kinase 1 (AKT1), tumor necrosis factor (TNF), mitogen-activated protein kinase 1 (MAPK1), MAPK3, vascular endothelial growth factor A (VEGFA), epidermal growth factor receptor (EGFR), etc.; GO function and KEGG pathway enrichment analysis showed that there were 1096 biological processes related to the intervention of Gualou Banxia Xiebai Decoction on COPD, such as inflammation, cytosol, enzyme binding, etc., and 125 related signal pathways such as cancer pathways, TNF signaling pathway, prostate cancer, hypoxia-inducible factor 1 signaling pathway, neuroactive ligand-receptor interaction, etc. The experimental results of zebrafish inflammation model showed that Gualou Xiebai Banxia Decoction significantly reduced IL-6, B-cell lymphoma-2 (BCL2) and EGFR mRNA expressions (P < 0.05), reduced Caspases 8 (CASP8) mRNA expression. Conclusion Gualou Xiebai Banxia Decoction may regulate multiple signal pathways by acting on targets such as EGFR, IL-6, BCL2, and CASP8, thereby exerting a therapeutic effect on COPD.

R285.5

江苏省自然科学基金面上项目（BK20201403）；江苏省高校自然科学基金重大项目（19KJA320002）；江苏省第十六批“六大人才高峰”计划（JNHB-066）；江苏省青蓝工程项目；江苏省高等学校大学生创新创业训练计划项目（202010315047Y）