| 摘要: |
| 目的:通过网络药理学以及分子对接技术来研究活血通降方治疗反流性食管炎的分子靶点及作用机制。方法:通过检索TCMSP 数据库获取活血通降方中7 味中药相关化学成分和作用靶点；结合GeneCards 数据库筛选反流性食管炎疾病主要靶点；利用Venny2.1 软件筛选活血通降方活性成分与反流性食管炎的共同作用靶点；提交二者交集靶点至STRING 平台，分析二者的蛋白质互作网络；利用DAVID 平台对其进行基因本体(GO)分析和通路富集(KEGG)分析。利用Cytoscape3.8.2 和String 数据库构建“药物活性成分-靶点”网络、蛋白质相互作用(PPI) 网络、“活性成分-作用靶点-通路”网络以及利用Cytoscape3.8.2 软件对该网络进行拓扑分析。利用分子的对接技术，由Autodock Vina 实现核心成分白细胞介素(IL)-6 与关键靶点分子对接。结果:本研究共筛选出活血通降方119 个活性成分及相应靶点268 个。反流性食管炎潜在作用靶点89 个。经Cytoscape 拓扑分析得到STAT3、TP53、JUN、AKT1、IL6、TNF 等17 个核心靶点，槲皮素、木犀草苷、山奈酚、黄芩素、柚皮素等20个核心活性成分。生物信息学富集分析中共获得711 个GO 条目，其中包括571 个生物过程(biological process，BP)、53 个细胞组成(cellular component，CC)、87 个分子功能(molecular function，MF)。KEGG 通路富集分析得到106 条通路，主要涉及癌症通路(pathways in cancer)、HIF-1 信号传导途径(HIF-1 signaling pathway)、TNF 信号传导途径(TNF signaling pathway)等。利用分子对接技术发现黄芩苷元、柚皮素、川陈皮素与IL-6 靶点有较强的亲和能力。结论:活血通降方通过降低炎症通路的激活，导致炎症因子分泌减少，从而起到修复食管黏膜炎症的作用。系统性揭示了活血通降方多途径、多靶点、多层次的调节作用，为活血通降方治疗反流性食管炎的临床应用研究提供了参考。 |
| 关键词: 活血通降方 网络药理学 分子对接 反流性食管炎 作用机制 |
| DOI：10.3969/j.issn.1007-6948.2024.05.023 |
| 投稿时间：2024-02-14 |
| 基金项目:国家自然科学基金(82274253、82074213、81573737) |
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| Molecular mechanism of Huoxue Tongjiang decoction in the treatment of reflux esophagitis based on network pharmacology and molecular docking |
| LIU Lei,GUO Zheng,TANG Yan-ping |
| Department of Gastroenterology 2, Nankai Hospital, Tianjin300170, China |
| Abstract: |
| Objective The clinical effect of Huoxue Tongjiang decoction (HTD)in the treatment of reflux esophagitis(RE) is satisfactory. To explore the molecular mechanism of HTD in the treatment of reflux esophagitis based on network pharmacology and molecular docking technology. Methods The chemical constituents and targets of 7 Chinese medicines in HTD were obtained by searching TCMSP database. GeneCards database was used to screen the main targets of reflux esophagitis. Venny2.1 software was used to screen the targets of the active components of HTD and reflux esophagitis. The two intersection targets were submitted to STRING platform to analyze the protein interaction network of the two. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed by DAVID platform. Cytoscape3.8.2 and String database were used to construct the "drug active component-target" network, protein interaction (PPI)network and "active component-action target-pathway" network, and Cytoscape3.8.2 software was used to analyze the network topologically. By using molecular docking technology, Autodock Vina realized the docking between core component IL -6 and key target molecules. Results A total of 119 active components and 268 corresponding targets of HTD were screened out in this study. There were 89 potential targets of reflux esophagitis. Cytoscape topological analysis revealed 17 core targets including STAT3, TP53, JUN, AKT1,IL6 and TNF, and 20 core active components including quercetin, luteolin, kaempferol, baicalin and naringin. A total of 711 GO items were obtained by bioinformatics enrichment analysis, including 571 biological processes(BP), 53 cellular component (CC) and 87 molecular functions (MF). KEGG pathway enrichment analysis revealed 106 Pathways, mainly involving Pathways in cancer, HIF-1 signaling Pathway, TNF signaling Pathway, etc. By molecular docking technique, baicalin, naringin and cyrrhizin showed strong affinity with IL-6 target. Conclusion The mechanism of action of HTD with multiple components, multiple targets and multiple pathways was systematically revealed, which provided a reference for the clinical application of HTD in the treatment of reflux esophagitis. |
| Key words: Huoxue Tongjiang decoction network pharmacology molecular docking reflux esophagitis |
