基于网络药理学和分子对接探讨丹参酮ⅡA治疗肺栓塞的分子机制

Research on the molecular mechanism of Tanshinone ⅡA in the treatment of pulmonary embolism based on network pharmacology and molecular docking

目的 基于网络药理学和分子对接探讨丹参酮ⅡA治疗肺栓塞(PE)的分子机制,揭示其相关生物学靶点和信号通路。方法 通过网络数据库获得PE和丹参酮ⅡA的相关靶点,取交集后获得交叉靶点。利用STRING数据库分析蛋白质-蛋白质相互作用(PPI)网络,之后应用Cytoscape软件及其插件获得丹参酮ⅡA抗PE的核心靶点。利用R语言对核心靶点进行基因本位(GO)功能、京都基因和基因组百科全书(KEGG)通路富集分析,分别探索其生物学功能和主要信号途径。运用Cytoscape软件构建可视化网络图,通过分子对接验证丹参酮ⅡA与核心靶点之间的相互作用。结果 经筛选共获得131个丹参酮ⅡA治疗PE的交叉靶点,应用CytoHubba插件筛选得到位居前10位的核心靶点基因,分别是类固醇受体辅助活化因子(SRC)、蛋白酪氨酸磷酸酶非受体型11(PTPN11)、雌激素受体1(ESR1)、信号转导及转录激活因子1(STAT1)、TP53、AP-1转录因子亚单位(JUN)、蛋白激酶B1(PKB1,又称AKT1)、丝裂原活化蛋白激酶1(MAPK1)、热休克蛋白90AA1(HSP90AA1)、丝裂原活化蛋白激酶14(MAPK14)。GO功能和KEGG通路富集分析结果显示,10个核心基因参与多种重要的信号通路。分子对接结果显示,丹参酮ⅡA与10个核心靶点基因的结合活性均较高。结论 通过网络药理学和分子对接揭示了丹参酮ⅡA治疗PE的核心靶点和信号通路,但仍需进一步研究。

Objective To explore the molecular mechanism of Tanshinone ⅡA in the treatment of pulmonary embolism(PE) based on network pharmacology and molecular docking model, and reveal its underlying biological targets and signaling pathways. Method The relevant targets of PE and Tanshinone ⅡA were obtained through the network database, and the targets were obtained after taking the intersection. The STRING database was used to analyze the protein-protein interaction(PPI) network, and then the Cytoscape software and its plug-in were used to obtain the core target of tanshinone ⅡA anti-PE. The R language was used to perform the gene ontology(GO) function and the Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis of the core targets to further explore their biological functions and main signaling pathways, respectively. Cytoscape software was used to construct a visualized network diagram, and the interaction between Tanshinone ⅡA and the core target was verified by molecular docking. Result A total of 131 cross-targets of Tanshinone ⅡA in the treatment of PE were obtained after screening. The Cyto Hubba plug-in was used to screen these targets to obtain the top 10 core target genes, which were steroid receptor coactivator(SRC), protein tyrosine phosphatase non-receptor type 11(PTPN11), estrogen receptor 1(ESR1), signal transducer and activator of transcription 1(STAT1), TP53, AP-1 transcription factor subunit(JUN), protein kinase B1(PKB1, also known as AKT1), mitogen-activated protein kinase 1(MAPK1), heat shock protein 90 alpha family class A member 1(HSP90AA1), and mitogen-activated protein kinase 14(MAPK14). The results of GO function and KEGG pathway enrichment analysis showed that 10 core genes were involved in various important signaling pathways. The molecular docking results presented that Tanshinone ⅡA had high binding activity to 10 core target genes. Conclusion This study revealed the core targets and signaling pathways of Tanshinone ⅡA for PE through network pharmacology and molecular docking. However, there is an unmet need for further study.