半夏泻心汤治疗脓毒症胃肠功能障碍的作用机制研究：基于网络药理学及分子对接技术

Research on the Mechanism of Banxia Xiexin Decoction in Treating Gastrointestinal Dysfunction in Sepsis: Based on Network Pharmacology and Molecular Docking Technology

摘要: 目的：通过网络药理学探讨半夏泻心汤治疗脓毒症胃肠功能障碍的作用机制。方法：通过PubChem、TCMSP、Swiss Target Prediction数据库检索并筛选半夏泻心汤组方药物活性成分及作用靶点，通过人类基因GeneCards数据库及Venny网站检索并筛选脓毒症胃肠功能障碍的靶点基因，通过Venny网站预测半夏泻心汤治疗脓毒症胃肠功能障碍的潜在治疗靶点，通过STRING 12.0数据库及Cytoscape 3.10.2软件构建药物与疾病蛋白互作网络、“中药–活性成分–潜在治疗靶点–疾病”网络，筛选网络中核心靶点及关键活性成分，对潜在治疗靶点进行富集分析，采用MOE软件进行分子对接，探究核心靶点与关键活性成分的相互作用。结果：获得半夏泻心汤活性成分177个，作用靶点1186个；脓毒症胃肠功能障碍靶点基因2918个；半夏泻心汤与脓毒症胃肠功能障碍潜在治疗靶点470个；通过网络拓扑分析得到半夏泻心汤治疗脓毒症胃肠功能障碍核心靶点AKT1、TNF、IL6、GAPDH和关键活性成分7-Methoxy-2-methyl isoflavone、1-Monolinolein等；KEGG通路富集分析得到190条信号通路，其中Pathways in cancer、Lipid and atherosclerosis等为主要信号通路；分子对接结合能良好。结论：半夏泻心汤治疗脓毒症胃肠功能障碍具有多个成分、靶点和通路的治疗特点，为进一步药物应用及临床实验研究提供了理论依据。

Abstract: Objective: To explore the mechanisms of Banxia Xiexin Decoction in treating gastrointestinal dysfunction in sepsis through network pharmacology. Methods: The active drug ingredients and targets of Banxia Xiexin Decoction formula were retrieved and screened through TCMSP, PubChem and Swiss Target Prediction databases, the target genes of gastrointestinal dysfunction in sepsis were retrieved and screened through the human gene GeneCards database and Venny website, and the potential therapeutic targets of Banxia Xiexin Decoction for gastrointestinal dysfunction in sepsis are predicted by Venny website. Through the STRING 12.0 database and Cytoscape 3.10.2 software, the PPI network and the “traditional Chinese medicine-active ingredient-potential therapeutic target-disease” network were constructed, the core targets and key active ingredients were selected from the network, and the potential therapeutic targets were enrichment analyzed. MOE software was used for molecular docking to investigate the interactions between the core targets and key active components. Results: A total of 177 active components and 1186 action targets of Banxia Xiexin Decoction were identified; 2918 target genes related to sepsis-induced gastrointestinal dysfunction were obtained; and 470 potential therapeutic targets for the treatment of sepsis-induced gastrointestinal dysfunction with Banxia Xiexin Decoction were identified. The core targets of Banxia Xiexin Decoction in the treatment of gastrointestinal dysfunction in sepsis were obtained through network topology analysis, such as AKT1, TNF, IL6 and GAPDH, and the key active ingredients 7-Methoxy-2-methyl isoflavone and 1-Monolinolein. 190 signaling pathways were enriched by KEGG pathway enrichment analysis, with Pathways in cancer, Lipid and atherosclerosis being the main signaling pathways; the molecular docking results showed good binding affinity. Conclusion: Banxia Xiexin Decoction has the characteristics of multiple components, targets, and pathways in treating gastrointestinal dysfunction in sepsis, providing theoretical basis for further drug application and clinical experimental research.