基于网络药理学探讨鹿角方治疗慢性心力衰竭的作用机制

The Mechanism of Lujiao Prescription in Treating Chronic Heart Failure Based on Network Pharmacology

目的 利用网络药理学方法对鹿角方与慢性心力衰竭(CHF)的交集靶点进行基因功能和通路富集分析,建立鹿角方成分-靶点-通路网络图,探讨鹿角方治疗慢性心力衰竭的作用机制。方法 通过PubChem数据库获取鹿角方活性成分的2D化学结构式,采用SwissTargetPrediction预测成分的潜在靶点;结合GeneCards、OMIM数据库获取慢性心力衰竭疾病靶点;通过Venn图获得药物-疾病的交集靶点。利用STRING在线数据库进行蛋白-蛋白互作(PPI)网络的构建与分析。利用David数据库对交集靶点进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析。通过Cytoscape 3.7.2构建“成分-靶点-通路”网络图,分析鹿角方治疗慢性心力衰竭的可能靶点及作用机制。结果 鹿角方的主要作用靶点71个,其中47个靶点与慢性心力衰竭密切相关。通过PPI网络分析筛选出9个关键靶点。GO功能富集分析显示:鹿角方主要参与的生物过程为氧化还原反应、缺氧反应、丝裂原活化蛋白激酶(MAPK)的正调控等。KEGG通路富集分析结果显示:鹿角方发挥治疗作用的通路包括胰岛素抵抗通路、甲状腺激素信号通路、血管平滑肌收缩通路、血管内皮生长因子(VEGF)信号通路。结论 鹿角方通过多靶点、多通路、多机制发挥药物功效,可延缓慢性心力衰竭的发生发展。

Objective To explore a network diagram of components-target-pathways using the network pharmacology method, to analyze the gene function and pathway enrichment of the intersection target and explore the mechanism of Lujiao Prescription in the treatment of chronic heart failure(CHF).Methods Obtaining the 2D chemical structure of active ingredient of Lujiao Prescription through PubChem database, to predict potential targets of the ingredient by SwissTargetPrediction.Combined with GeneCards and OMIM databases, CHF disease targets, and obtaining the intersection between drug and diseases through Venn platform were obtained.Using STRING online database protein-protein interaction(PPI) network were constructed and analyzed.With the David database, Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis of the intersection targets were performed.Finally, the "components-target-pathway" network diagram were contracted by Cytoscape 3.7.2,and to explore the possible targets and mechanism of Lujiao Prescription in the treatment of CHF.Results There were 71 main targets of Lujiao Prescription, 47 of which were closely related to CHF.Nine key targets were selected by PPI network analysis.GO enrichment analysis showed that Lujiao Prescription was mainly involved in biological processes such as redox reaction, hypoxia response, and positive regulation of mitogen activated protein kinase(MAPK).The results of KEGG enrichment analysis showed that the therapeutic pathway of Lujiao Prescription might be related to the insulin resistance pathway, thyroid hormone signaling pathway, vascular smooth muscle contraction pathway, and vascular endothelial growth factor signaling pathway.Conclusion Lujiao Prescription could delay the occurrence and development of chronic heart failure through multi-target, multi-pathway and multi-mechanism.