世界中医药

目的：运用网络药理学方法探讨炙甘草汤治疗心律失常的作用机制。方法：运用中药系统药理数据库与分析平台(TCMSP)和BATMAN-TCM数据库，筛选出炙甘草汤有效成分及其作用靶点。通过GeneCards、OMIM数据库筛选出心律失常的疾病靶点，并与中药靶点合并取交叉靶点，采用String数据库构建靶点蛋白质-蛋白质相互作用（PPI）网络，并运用Cytoscape 3.7.2筛选关键基因，同时借助CytoNCA插件进行拓扑分析；运用Bioconductor数据库及RX64 4.0.0软件对交集基因进行基因本体（GO）富集分析和京都基因和基因组百科全书（KEGG）通路富集分析。利用swissdock在线分子对接工具对蛋白质-蛋白质相互作用（PPI）网络中的核心蛋白与核心化合物分子进行分子对接。结果：筛选出171个化合物及4 090个靶点，得到关于心律失常疾病靶点435个；PPI结果显示，Degree值排名前6的基因分别为：INS、KCNH2、SCN5A、CAV3、GJA1、TNNI3；拓扑分析显示Degree排名前5的基因分别为：EGFR、HSPA8、NTRK1、ESR1、HSP90AA1；分子对接结果显示：炙甘草汤的大多数活性成分和关键靶点的结合率较强，其结合能最低为SCN5A与Lysine、KCNH2与Gamma-Aminobutyric Acid；GO富集分析显示炙甘草汤治疗心律失常与心脏收缩、心脏肌肉收缩、心的过程、横纹肌收缩、心脏收缩调节等有关。KEGG富集分析显示心肌细胞的肾上腺素能信号、肥厚型心肌病、cGMP-PKG信号通路、扩张型心肌病相关。结论：炙甘草汤治疗心律失常具有多成分、多靶点、多途径的特点。

English Summary:

To explore the mechanism of Zhigancao Decoction in treating arrhythmia based on network pharmacology.Methods:The active ingredients and targets of Zhigancao Decoction were screened out from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and BATMAN-TCM,and the disease targets of arrhythmia were screened out through GeneCards and OMIM.The common targets of the drug and the disease were obtained.String was used to construct a protein-protein interaction(PPI) network of targets,and Cytoscape 3.7.2 was used to screen key genes,which underwent topological data analysis by CytoNCA plug-in.Bioconductor and RX64 4.0.0 were adopted for GO enrichment and KEGG pathway enrichment analyses of common genes.The core proteins were subjected to molecular docking with core compound molecules in the PPI network using SwissDock.Results:A total of 171 compounds and 4 090 targets were screened out,and 435 targets related to arrhythmia were obtained.PPI results showed that in terms of degree,the top 6 genes were INS,KCNH2,SCN5A,CAV3,GJA1,and TNNI3.Topological data analysis revealed that in terms of degree,the top 5 genes were EGFR,HSPA8,NTRK1,ESR1,and HSP90AA1.Molecular docking results showed that most of the active ingredients and key targets of Zhigancao Decoction had high binding rates,with the lowest binding energy of SCN5A to lysine and KCNH2 to γ-aminobutyric acid.GO enrichment analysis showed that the therapeutic effect of Zhigancao Decoction was related to heart contraction,heart muscle contraction,heart process,striated muscle contraction,and heart contraction regulation.KEGG enrichment analysis showed that the therapeutic effect of Zhigancao Decoction was associated with adrenergic signal in cardiomyocytes,hypertrophic cardiomyopathy,cGMP-PKG signaling pathway,and dilated cardiomyopathy.Conclusion:Zhigancao Decoction is characterized by multi-component,multi-target,and multi-pathway in the treatment of arrhythmia.

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