| 摘要: |
| 目的：利用网络药理学和分子对接方法，探索大黄-白及-三七在治疗肝硬化伴消化道出血中的主要活性成分、关键作用靶点及机制。方法：通过TCMSP、Pubchem和SwissTargetPrediction数据库获取大黄、白及、三七的活性成分及靶点，同时从GeneCards和DisGeNET数据库中搜集与肝硬化伴消化道出血相关的靶点。利用Venn图找出药物-疾病交集靶点，利用STRING建立蛋白质-蛋白质相互作用网络，并使用Cytoscape 3.10.1进行可视化分析。通过Metascape数据平台完成基因本体（GO）功能和京都基因与基因组百科全书（KEGG）通路富集分析，分子对接验证则采用AutoDock Tools 1.5.6和PyMoL 2.4.0软件。结果：共获得大黄-白及-三七的有效成分32个，预测到523个潜在靶点，获得1011个肝硬化伴消化道出血靶点，得到中药-疾病交集基因149个。中药的主要活性成分有2，3，4，7-四甲氧基菲、泽兰黄醇、槲皮素、3-（对羟基苄基）-4-甲氧基-9，10-二氢菲、甘草素等，主要通过非受体酪氨酸激酶、信号转导及转录激活因子3、丝氨酸/苏氨酸激酶 1、磷酸肌醇 3-激酶调节亚基 1、磷脂酰肌醇 4，5-二磷酸 3-激酶催化亚基 α等关键靶点和磷脂酰肌醇-3-激酶/丝苏氨酸蛋白激酶、缺氧诱导因子1、Ras相关蛋白1、血管内皮生长因子等信号通路发挥治疗肝硬化伴消化道出血的作用。分子对接发现活性成分2，3，4，7-四甲氧基菲、槲皮素与靶点SRC结合活性高且稳定。结论：大黄-白及-三七可能通过槲皮素、甘草素等成分，SRC等靶点和PI3K-Akt等通路协同治疗肝硬化伴消化道出血。 |
| 关键词: 肝硬化 消化道出血 大黄 白及 三七 网络药理学 分子对接 |
| DOI： |
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| Mechanism of action of Rheum officinale-Rhizoma Bletillae-Panax notoginseng in treatment of liver cirrhosis with gastrointestinal bleeding：A study based on network pharmacology and molecular docking |
| SHI Yusha,MU Yuhong,JIANG Yue |
| (Wenzhou Hospital of Traditional Chinese Medicine，Zhejiang Chinese Medical University，Wenzhou 325000，Zhejiang，China;The First Affiliated Hospital of Wenzhou Medical University，Wenzhou 325000，Zhejiang，China) |
| Abstract: |
| Objective：To investigate the main active components，key action targets，and mechanism of action of Rheum officinale-Rhizoma Bletillae-Panax notoginseng in the treatment of liver cirrhosis with gastrointestinal bleeding based on network pharmacology and molecular docking.Methods：TCMSP，Pubchem，and SwissTargetPrediction databases were used to obtain the active components and targets of Rheum officinale，Rhizoma Bletillae，and Panax notoginseng，and GeneCards and DisGeNET databases were used to obtain the targets associated with liver cirrhosis with gastrointestinal bleeding.The Venn diagram was used to obtain drug-disease intersecting targets，STRING database was used to establish a protein-protein interaction network，and Cytoscape 3.10.1 was used for visual analysis.Metascape data platform was used to perform the gene ontology functional enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis，and AutoDock Tools 1.5.6 and PyMoL 2.4.0 were used to perform molecular docking.Results：A total of 32 effective constituents were obtained for Rheum officinale-Rhizoma Bletillae-Panax notoginseng，and 523 potential targets were obtained，as well as 1011 targets associated with liver cirrhosis with gastrointestinal bleeding and 149 drug-disease intersecting targets.The main active components of the drugs included 2，3，4，7-tetramethoxyphenanthrene，eupatin，quercetin，3-(p-hydroxybenzyl)-4-methoxy-9，10-dihydrophenanthrene，and glycyrrhizin，which exerted a therapeutic effect on liver cirrhosis with gastrointestinal bleeding through the targets including non-receptor tyrosine kinase，signal transducer and activator of transcription 3，serine/threonine kinase 1，phosphoinositide-3-kinase regulatory subunit 1，phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit α and the signaling pathways including phosphatidylinositol 3-kinase/serine-threonine protein kinase，hypoxia-inducible factor 1，and vascular endothelial growth factor.Molecular docking showed that the active components 2，3，4，7-tetramethoxyphenanthrene and quercetin had high and stable binding activity to the target SRC.Conclusion：Rheum officinale-Rhizoma Bletillae-Panax notoginseng exerts a synergistic therapeutic effect on liver cirrhosis with gastrointestinal bleeding through the components including quercetin and glycyrrhizin，the targets including SRC，and the signaling pathways including PI3K-Akt. |
| Key words: liver cirrhosis gastrointestinal bleeding Rheum officinale Rhizoma Bletillae Panax notoginseng network pharmacology molecular docking |
