基于网络药理学研究龙血竭总黄酮治疗心肌缺血再灌注损伤的作用机制

Mechanism of Sanguis draconis flavones in treatment of myocardial ischemia-reperfusion injury based on network pharmacology

目的:通过网络药理学和分子对接的方法预测龙血竭总黄酮(SDF)防治心肌缺血再灌注损伤(MIRI)的作用机制。方法:利用文献检索收集SDF的主要化学成分,通过SwissTargetPrediction和TargetNet数据库进行关键成分靶点筛选。通过GeneCards、OMIM、TTD和PharmGkb数据库进行疾病靶点筛选,将靶点交集并通过Cytoscape构建“药物-关键成分-靶点”网络关系图,通过Cytoscape软件进行可视化并分析得到核心靶点。通过Metascape平台进行GO功能和KEGG通路富集分析。依据AutoDock Vina软件和PyMol对核心化合物与核心靶点进行分子对接。动物实验进一步探索SDF的药效机制。结果:SDF的活性成分有龙血素A和龙血素B等,映射391个靶点。从数据库共获得MIRI疾病靶点3096个,进行交集后获得172个交集靶点,分析得到核心靶点56个。核心的关联途径包含肿瘤途径以及细胞死亡信号途径等。分子对接证明了关键构成部分与关键靶点的结合活力强。动物实验发现SDF能够有效防治MIRI,显著抑制花生四烯酸15-脂氧合酶的mRNA和蛋白表达,减少MIRI后的心肌梗死面积。结论:SDF可能对MIRI治疗有一定的积极意义,其机制可能与ALOX15因子的调控有关。

AIM:To predict the mechanism of Sanguis draconis flavones(SDF)in the prevention and treatment of myocardial ischemia reperfusion injury(MIRI)based on network pharmacology and molecular docking methods.METHODS:The main chemical constituents of SDF were collected through literature search,and the targets of key constituents were screened by using the SwissTargetPrediction and TargetNet databases.Disease targets were also screened based on GeneCards,OMIM,TTD and PharmGkb databases,then targets were intersected with Cytoscape to construct the"drug-key constituent-target"network diagram,and the core target was obtained through visualization and analysis by Cytoscape software.Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses were analyzed by the Metascape platform.By utilizing AutoDock Vina software and Pymol,molecular docking between core compounds and core targets was carried out.Further,animal experiments were performed to explore the pharmacodynamic mechanism of SDF.RESULTS:The active constituents of SDF included loureirin B and loureirin A,which were mapped to 391 targets.A total of 3096 MIRI disease targets were obtained from the database,after intersection,172 intersection targets were obtained,and 56 core targets were acquired through analysis.The core related pathways included the cancer pathway and cell death signaling pathway.The results of molecular docking verified the strong binding activity between key constituents and key targets.Animal experiments demonstrated that SDF effectively prevented and treated MIRI,significantly inhibited the arachidonic acid 15-lipoxygenase(ALOX15)mRNA and protein expression,and reduced the myocardial infarction size after MIRI.CONCLUSION:SDF may play a positive role in the treatment of MIRI,which may be related to the regulation of the ALOX15 factor.