基于网络药理学探讨黄芪治疗慢性心力衰竭作用机制

Mechanistic Analysis of Astragali Radix in the Treatment of Chronic Heart Failure Based on Network Pharmacology

目的基于网络药理学探讨黄芪治疗慢性心力衰竭可能的作用机制。方法运用中药系统药理数据库和分析平台(TCMSP)与文献挖掘获取黄芪的有效化学成分及作用靶点。在GeneCards、OMIM数据库搜索慢性心力衰竭的靶点。采用Cytoscape 3.2.1软件构建黄芪活性成分-CHF-靶点网络模型。运用String数据库构建蛋白质间相互作用网络。借助DAVID在线工具进行疾病-药物交集靶基因的基因本体论(GO)富集分析和京都基因与基因组百科全书(KEGG)通路富集分析。结果通过筛选得到黄芪21个化学成分,黄芪治疗慢性心力衰竭的预测靶点有145个。网络分析结果表明,得出黄芪主要涉及RNA聚合酶Ⅱ启动子转录的正调控、对炎症细胞因子的反应、过氧化氢的合成、调节平滑肌收缩等生物过程,通过调节肿瘤坏死因子、细胞凋亡、Toll样受体、分裂原激活的蛋白激酶(MAPK)等主要信号通路来发挥治疗慢性心力衰竭的作用。结论通过网络药理学方法初步揭示了黄芪治疗慢性心力衰竭的多成分、多靶点、多通路的作用机制,为黄芪的实验研究和临床应用提供了科学依据。

Objective To explore the possible mechanism of Astragali Radix in the treatment of chronic heart failure by the network pharmacology. Methods The effective chemical ingredients and target gene of Astragali Radix were obtained through TCMSP and literature search. GeneCards and OMIM were used to predict and screen the targets of chronic heart failure. The Cytoscape 3.2.1 software was used to construct the active components-CHF-targets network of Astragali Radix. The protein interactions network was constructed using the String database. With DAVID Online Tools,Gene Ontology(GO)Analysis of Disease-Drug Intersection Target Genes and enrichment analysis of KEGG pathway were conducted. Results 21 chemical components of Astragali Radix were obtained by database,145 potential targets for the treatment of chronic heart failure were obtained. The network analysis results showed that positive regulation of RNA polymerase II promoter transcription,response to inflammatory cytokines,synthesis of hydrogen peroxide,regulation of smooth muscle contraction and other biological processes were mainly involved by adjusting tumor necrosis factor,apoptosis,Toll-like receptors,MAPK and other signaling pathways to exert its treatment of chronic heart failure. Conclusion This study preliminarily revealed the mechanism of multicomponent,multi-target and multi-channel treatment of Astragali Radix in the treatment of chronic heart failure by network pharmacology,which provided a scientific basis for the experimental research and clinical application of Astragali Radix.