基于网络药理学的丹皮-赤芍-黄连治疗快速性心律失常的物质基础及作用机制研究

Study on the Material Basis and Molecular Mechanism of"Danpi-Chishao-Huanglian"against Tachyarrhythmia Based on Network Pharmacology

目的基于网络药理学探寻丹皮-赤芍-黄连治疗快速性心律失常的物质基础和作用机制。方法借助中药系统药理学分析平台(TCMSP)检索中药丹皮、赤芍、黄连的化学成分和作用靶点,根据口服生物利用度和类药性筛选化学成分并获得相应成分的靶点,通过检索GeneCards在线数据库获取与快速性心律失常相关靶点,利用Venny 2.1软件得到药物-疾病之间的共同靶点,将共同靶点导入STRING 10.5数据库进行蛋白互作网络分析,运用Cytoscape 3.7.1构建药物-成分-靶点-疾病网络,最后通过DAVID 6.8在线数据库进行基因本体(GO)分析和京都基因及基因组百科全书(KEGG)通路富集分析。结果从丹皮-赤芍-黄连中筛选得到14个潜在化学成分,共涉及16个靶点。通过GO分析得到48个生物过程(BP)、10个细胞组分(CC)和8个分子功能(MF)。通过KEGG分析得出富集通路13条。结论丹皮-赤芍-黄连治疗快速性心律失常具有多成分、多靶点、多通路的特点,槲皮素、丹皮酚、芍药苷、小檗碱等可能为丹皮-赤芍-黄连发挥作用的关键成分,其通过作用于NOS3、KCNH2、SCN5A、ADRB2、IL6等靶点,影响多种离子通道的活性和心肌细胞膜的去极、复极过程以及cGMP-PKG信号通路、心肌细胞肾上腺素能信号转导通路和钙信号通路,从而发挥治疗快速性心律失常的作用。

Objective To explore the material basis and molecular mechanism of Danpi-Chishao-Huanglian(DP-CS-HL)in the treatment of tachyarrhythmia based on network pharmacology.Methods Traditional Chinese Medicine Systems Pharmacology Analysis Platform(TCMSP)was used to search the chemical components and targets of DP-CS-HL.The chemical components were screened according to oral bioavailability and drug like propertie,and the corresponding targets were obtained.The related targets of tachyarrhythmia were obtained by searching the GeneCards online database.The common target between drugs and diseases was obtained by Venny 2.1 software.The protein protein interaction(PPI)network analysis was carried out by importing STRING 10.5 database,and the drug-component-target-disease network was constructed by Cytoscape 3.7.1.Finally,Gene ontology(GO)analysis of common genes and enrichment analysis of gene encyclopedia kyoto encyclopedia of genes and genomes(KEGG)pathway were carried out using DAVID 6.8 online tool.Results Fourteen potential chemical constituents were screened from DP-CS-HL,involving 16 targets.Forty-eight biological processes(BP),10 cell components(CC),and 8 molecular functions(MF)were obtained by GO analysis.Thirteen enrichment pathways were obtained through KEGG analysis.Conclusion DP-CS-HL had the characteristics of multi-component,multi-target,and multi-channel in the treatment of tachyarrhythmia.Quercetin,paeonol,paeoniflorin,and berberine might be the key components of DP-CS-HL.By acting on NOS3,KCNH2,SCN5A,ADRB2,and IL6,DP-CS-HL affects the activity of various ion channels,depolarization and repolarization of cardiomyocytes membrane,cGMP-PKG signal pathway,adrenergic signal transduction pathway,and calcium signal pathway,so as to play a role in the treatment of tachyarrhythmia.