基于网络药理学和分子对接探讨小青龙汤合人参汤防治高原肺水肿的作用机制

Exploring Mechanism of Xiaoqinglong Combined with Ginseng Decoction in Preventing High Altitude Pulmonary Edema Based on Network Pharmacology and Molecular Docking

摘要: 目的：基于网络药理学和分子对接技术分析小青龙汤合人参汤抗高原肺水肿的作用机制。方法：通过TCMSP获取小青龙汤合人参汤主要活性成分及其靶点；通过OMIM、Genecards和DisGeNET数据库获取高原肺水肿主要作用靶点；通过Venn Diagram得到小青龙汤合人参汤与高原肺水肿的共同靶点；利用String数据库获得数据，用Cytoscape3.9.1建立蛋白质互作(PPI)网络；采用David数据库分析生物过程及信号通路，采用Cytoscape3.9.1软件构建“活性成分–靶点”网络，并运用AutoDock及Pymol对关键靶点与相应活性成分进行分子对接验证。结果：从小青龙汤合人参汤中筛选得到159种活性成分及329个作用靶点，与887个高原肺水肿相关靶点取交集，得到62个共同靶点，GO功能富集分析中生物过程(BP)得到214条，分子功能(MF)得到25条，细胞成分(CC)得到13条；KEGG信号通路富集分析获得93条。结论：小青龙汤和人参汤防治高原肺水肿的核心活性成分为槲皮素、山柰酚、β-谷甾醇等，关键靶点为IL6、TNF、VEGFA等；小青龙汤合人参汤防治高原肺水肿主要涉及HIF-1信号传导途径、脂质和动脉硬化、Toll样受体信号通路、TNF信号传导途径等。

Abstract: Objective: To analyze the mechanism of Xiaoqinglong combined with Ginseng decoction in prevent-ing high-altitude pulmonary edema based on network pharmacology and molecular docking tech-nology. Methods: The main active components and their targets of Xiaoqinglong combined with Ginseng decoction were obtained through the TCMSP, screen the active components of traditional Chinese medicine; obtain the main targets of high altitude pulmonary edema through OMIM, Gene-cards, drugbank databases; obtain the common targets of Xiaoqinglong combined with ginseng de-coction and high altitude pulmonary edema through Venn Diagram; use cytocaspe3.9.1 software to carry out Protein-protein interaction network (PPI) analysis, to construct PPI network; use David database to analyze biological processes and signaling pathways, use Cytoscape3.9.1 software to build an “active ingredient-target” network, and use AutoDock and Pymol performs molecular docking verification on key targets and corresponding active ingredients. Results: 159 active ingre-dients and 329 targets were screened from Xiaoqinglong combined with ginseng decoction, and 887 high-altitude pulmonary edema-related targets were intersected to obtain 62 common targets; in the functional enrichment analysis of GO, 214 biological processes (BP), 25 molecular functions (MF) and 13 cellular components (CC) were obtained. 93 KEGG signal pathways were obtained by en-richment analysis Conclusion Quercetin, kaempferol, β-sitosterol in Xiaoqinglong combined with Ginseng decoction may be the core compounds for treating diseases, and gene targets such as IL6, TNF, and VEGFA are the best target options for diseases. Xiaoqinglong combined with Ginseng de-coction may be involved in the HIF-1 signaling pathway, lipids and atherosclerosis, Toll-like recep-tor signaling pathway, and TNF signaling pathways in treating HAPE.