基于网络药理学分析三七总皂苷通过外泌体miR-21干预缺血性脑卒中作用机制

Analysis of the mechanism of Panax notoginseng saponins intervening ischemic stroke through exosome miR-21 based on network pharmacology

目的利用生物信息学方法探讨外泌体miR-21和三七总皂苷在缺血性脑卒中治疗的分子作用机制及调控网络。方法使用多个数据库查询三七总皂苷活性成分及靶基因、外泌体miR-21和缺血性脑卒中的靶基因;对共同靶基因进行GO和KEGG分析,使用Cytoscape软件构建活性化合物-靶基因-信号通路网络图和PPI网络图,筛选核心基因。最后运用分子对接对活性化合物和主要靶点进行验证。结果获得三七总皂苷12个活性成分及47个共同靶基因。PPI网络构建得到10个核心基因:CASP3、EGFR、VEGFA、STAT3、HIF1A、ESR1、BCL2L1、HSP90AA1、PTGS2、MTOR。GO富集分析表明靶基因主要富集在凋亡过程的负调控、一氧化氮生物合成过程的正调控、RNA聚合酶Ⅱ启动子转录的正调控、细胞增殖的正调控生物学过程项目。KEGG富集分析表明,共同基因主要参与癌症中的蛋白聚糖、HIF-1信号通路、胰脏癌、肿瘤坏死因子信号通路等通路。分子对接表明主要活性成分与核心靶点有较强的结合能力。结论外泌体miR-21和三七总皂苷通过多靶点、多途径、多通路干预缺血性脑卒中,STAT3、VEGFA、HSP90AA1、BCL2L1、MAPK1是值得关注的靶基因,蛋白多糖与癌症通路是主要调控通路。

Objective To explore the molecular mechanism and regulatory network of exosome miR-21 and Panax notoginseng saponins in the treatment of ischemic stroke by bioinformatics.Methods The active components and target genes of Panax notoginseng saponins,target genes of exosome miR-21 and ischemic stroke were investigated by multiple databases.Common target genes were analyzed by GO and KEGG.Cytoscape software was used to construct active compound-target gene-signal pathway network map and PPI network map to screen core genes.Finally,molecular docking was used to verify the active compounds and main targets.Results This study obtained twelve active components and 47 common target genes of Panax notoginseng saponins.The PPI network was constructed to obtain 10 core genes:CASP3,EGFR,VEGFA,STAT3,HIF1A,ESR1,BCL2L1,HSP90AA1,PTGS2,MTOR.GO enrichment analysis showed that the target genes were mainly enriched in the biological processes of negative regulation of apoptosis,positive regulation of nitric oxide biosynthesis,positive regulation of RNA polymerase II promoter transcription,and positive regulation of cell proliferation.KEGG enrichment analysis showed that common genes were mainly involved in proteoglycan,HIF-1 signaling pathway,pancreatic cancer,tumor necrosis factor signaling pathway and other pathways in cancer.Molecular docking showed that the main active components had strong binding ability with the core target.Conclusion Exosome miR-21 and Panax notoginseng saponins intervene ischemic stroke through multiple targets,multiple approaches,and multiple pathways.STAT3,VEGFA,HSP90AA1,BCL2L1,and MAPK1 are target genes that deserve attention,and proteoglycan and cancer pathways are main regulatory pathways.