清心解瘀方调控巨噬细胞稳定动脉粥样硬化易损斑块的网络药理学研究

Study of Qingxin Jieyu Formula for Regulation of Vulnerable Atherosclerotic Plaques by Network Pharmacology

目的基于网络药理学研究的思路和方法探索清心解瘀方调控巨噬细胞稳定动脉粥样硬化(AS)易损斑块的潜在机制。方法利用GEO数据库下载编号为GSE41571的基因芯片,筛选出易损/破裂斑块与稳定斑块中巨噬细胞的差异表达基因899个,利用BATMAN-TCM平台检索出清心解瘀方中各味中药的活性成分187个,筛选出活性成分的潜在靶点基因1686个。取两者交集基因,利用Cytoscape 3.2.2软件构建“药物-活性成分-靶基因”网络,利用Metascape对基因功能和生物信号通路进行富集分析及数据可视化。结果清心解瘀方中5味中药的110种活性成分可作用于87个靶点基因,通过调控炎症细胞的迁移和增殖、脂质合成代谢、细胞程序性死亡和细胞吞噬等生物学过程,调控巨噬细胞脂质代谢、细胞迁移和吞噬、凋亡、自噬、铁死亡等信号通路,发挥稳定AS易损斑块的作用。结论初步阐释了清心解瘀方调控巨噬细胞稳定易损斑块的药效成分和潜在生物学机制,并提出调控巨噬细胞铁死亡可能是其稳定AS易损斑块的重要潜在途径。

Objective To explore possible mechanisms of Qingxin Jieyu Formula(QXJYF)in stabilizing vulnerable plaques by targeting macrophages with network pharmacological methods.Methods No.GSE41571 gene microarray data were downloaded from GEO database and 899 differentially expressed genes related to macrophages in ruptured plaques were screened out.BATMAN-TCM platform was used to search for active compounds in QXJYF and their target genes,187 active compounds and 1686 potential target genes were identified.Intersectional genes were identified and Metascape online tool was used to perform biological processes and pathways enrichment analysis.Cytoscape 3.2.2 software was used to construct a′medicine-compound-target gene′network.Results QXJYF might stabilize vulnerable plaques through 110 active compounds′regulation on 87 target genes.Biological processes involved leukocyte migration,regulation of lipid metabolic process,regulation of apoptotic signaling pathway,etc.Pathways involved metabolism of lipids,PI3K-Akt signaling pathway,ferroptosis,inflammatory cell migration and cytosis,etc.Conclusion This study points some novel potential active compounds and possible mechanisms of QXJYF′s effects in stabilizing vulnerable plaques by targeting macrophages,and suggest a hypothesis that macrophage ferroptosis might be an important factor in the formation of vulnerable plaques to provide clues for further research.