基于网络药理学和分子对接探讨三七治疗视网膜静脉阻塞的分子机制

Explore the Molecular Mechanism of Panax notoginseng on Retinal Vein Occlusion Based on Network Pharmacology and Molecular Docking

目的:探讨三七治疗视网膜静脉阻塞(RVO)的分子作用机制。方法:采用TCMSP数据库及文献补充获得三七的有效成分,并在Swiss Target Prediction收集其作用靶点;使用GeneCards等5个数据库检索RVO疾病靶点,并将三七成分靶点与RVO疾病靶点进行映射;利用STRING、Cytoscape 3.8.2软件构建蛋白-蛋白相互作用网络图,筛选出核心靶基因,对其进行GO和KEGG富集分析。最后,利用Sybyl-x 2.0软件进行分子对接验证。结果:筛选出三七有效成分10种,涉及354种蛋白。RVO的疾病靶点有181个,其中9个是三七治疗RVO的潜在靶点。“药物-活性成分-疾病-靶蛋白”相互作用网络中,核心作用靶点包括VEGFA、EGFR等;通过GO及KEGG富集分析,筛选出参与RVO主要生物学过程28种,相关信号通路18条。三七治疗RVO潜在的分子机制与纤溶等生物学过程密切相关。关键信号通路包括HIF-1信号通路、PI3K-Akt信号通路等。分子对接结果提示,三七主要活性成分DFV、Panaxydol等与VEGFA、EGFR等关键靶点有着较好的结合活性。结论:三七的多成分通过纤溶等多种生物学过程及HIF-1等多条生物学信号通路,多靶点、多通路、多效应作用于视网膜,进一步发挥治疗作用,而VEGFA、EGFR等可能是潜在作用靶点。

Objective:To explore the molecular mechanism of Panax notoginseng in the treatment of retinal vein occlusion(RVO).Methods:The active components of Panax notoginseng were screened by using TCMSP database and relative articles,and the corresponding active targets were collected by Swiss Target Prediction database.Then,GeneCards and other five databases were used to search RVO disease targets,and Panax notoginseng active targets were mapped to RVO genes.In addition,the network diagram of protein-protein interaction was constructed by Cytoscape 3.8.2 and STRING software,andthese core genes were selected for GO and KEGG enrichment analysis.Finally,molecular docking verification was performed by software Sybyl-x 2.0.Results:Ten active components of Panax notoginseng were screened,involving 354 proteins.There were 181 disease targets of RVO,among which 9 were potential targets of Panax notoginseng for the treatment of RVO.Furthermore,in the drug‐active‐component‐disease‐target protein interaction network,the core target genes included VEGFA,EGFR,etc.According to GO and KEGG enrichment analysis,28 biological processes and 18 signaling pathways related to RVO were screened out.The potential molecular mechanism of Panax notoginseng treatment of RVO was closely related to fibrinolysisand other biological processes.The key signaling pathways included HIF-1 signaling pathway,PI3K-Akt signaling pathway,etc.Molecular docking results also suggested that the main active compoents of DFVand panaxydol had good binding activity to key targets such as VEGFA,EGFR and other key targets.Conclusion:The several components of Panax notoginseng act on the retina through diff erent biological processes such as fibrinolysisand diff erent signaling pathways such as HIF-1,with multiple targets,multiple pathways and multiple eff ects,and further play a treatment role.So the VEGFA,EGFR,etc.,may be the potential therapeutic targets.