基于网络药理学探究益心泰方治疗心力衰竭的作用机制

Application of Network Pharmacology to Explore the Mechanism of Yi Xin Tai Formula in Treating Heart Failure

  • 摘要:
    目的应用网络药理学方法探讨益心泰方治疗心力衰竭潜在的作用机制,并通过Western blotting实验对相关靶点作初步验证。
    方法以心力衰竭为疾病模型,应用TCMSP数据库及其分析平台,根据OB和DL筛选益心泰方的活性成分,并预测出相应靶标;经HPO数据库检索心力衰竭的疾病靶标;然后在STRING数据库构建“益心泰成分−潜在靶标−心力衰竭”网络,通过Cytoscape软件将网络可视化,再根据D,CC和BC得到网络的关键节点,借助GATHER数据库平台对关键节点进行KEGG的基因功能富集分析。用缩窄腹主动脉法+ PTU 灌胃建立心衰兔模型,通过Western blotting法观察兔心肌组织TGF-β蛋白的病理改变及蛋白表达情况。
    结果“益心泰方成分−潜在靶标−心力衰竭”网络包含403个节点,关键节点136个,相关的KEGG通路10条,分别为黏着斑、细胞周期、MAPK信号通路、Toll样受体信号通路、细胞因子−细胞因子受体相互作用、Gap连接、黏附结、TGF-β信号通路、细胞凋亡、Wnt信号通路。心肌组织TGF-β蛋白表达明显降低。
    结论经网络药理学测算,益心泰方治疗心力衰竭可能与10个代谢通路有关,初步揭示了其作用的多成分-多靶点-多通路,以及复方君臣佐使配伍协同增效的作用特点。

     

    Abstract:
    ObjectiveTo explore the possible mechanism of Yi Xin Tai Formula (YXTF) in treating heart failure (HF) by network pharmacology method and to verify the related targets by western blotting.
    MethodsUsing the traditional Chinese medicine systems pharmacology (TCMSP) database with its analysis platform for HF as a disease model, the active ingredients of YXTF were filtered according to the oral bioavailability (OB) and drug-likeness (DL), and the corresponding targets were predicted. The disease targets of HF were retrieved by Human Phenotype Ontology (HPO) database. Then, “YXTF compounds - Targets - HF” network was constructed in the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, the network visualized through the Cytoscape software, and the key nodes of the network achieved according to Degree (D), Closeness Centrality (CC), and Betweenness Centrality (BC). Kyoto Encyclopedia of Genes and Genomes (KEGG) gene function enrichment analysis was carried out for the key nodes with the help of GATHER database platform. The rabbit model of HF was established by coarctation of the abdominal aorta and perfusion of propylthiouracil (PTU). The pathological changes and protein expression of transforming growth factor beta (TGF-β) protein were observed by western blotting.
    Results“YXTF compounds - Targets - HF” network consisted of 403 nodes, 136 key nodes and 10 related KEGG pathways that included focal adhesions, cell cycles, mitogen-activated protein kinase (MAPK) signaling pathways, Toll-like receptor signaling pathways, Cytokine-cytokine receptor interactions, Gap junctions, adherens junctions, TGF-β signaling pathways, apoptosis and Wnt signaling pathways, respectively. The expression of TGF-β protein in myocardium decreased significantly.
    ConclusionsAccording to the network pharmacology, the treatment of YXTF for HF might be related to 10 metabolic pathways. The effects of the multicompound-multitarget-multi pathways and the synergistic effect drawn from the compounds that act as the monarch, minister, adjuvant, guide medicines were revealed through this study.

     

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