基于网络药理学与分子对接探究沙库巴曲缬沙坦钠对抑制血管内膜增生治疗动静脉内瘘成熟障碍及狭窄的作用机制  

Based on network pharmacology and molecular docking to investigate the mechanisms of sacubitril valsartan sodium for the treatment of delayed maturation and stenosis of arteriovenous fistula through inhibition of intimal hyperplasia

作　　者：黎欣 覃新芳[1] 蓝雪化 LI xin;QIN Xin-fang;LAN Xue-hua(Department of Nephrology,The Affiliated Hospital of Guilin Medical University,Guilin 541001,China)

机构地区：[1]桂林医学院附属医院肾脏内科,桂林541001

出　　处：《中国血液净化》2025年第1期61-65,共5页Chinese Journal of Blood Purification

摘　　要：目的利用网络药理学及分子对接方法探讨沙库巴曲缬沙坦钠(sacubitril valsartan sodi-um,LCZ696)抑制血管内膜增生(intimal hyperplasia,IH)治疗动静脉内瘘成熟障碍及狭窄的分子靶点机制。方法通过Chemical Book平台及SwissTarget Prediction数据库获取LCZ696的有效成分及对应靶点;利用GeneCards及在线人类孟德尔遗传数据库收集IH靶点、Protain-Protain Interaction数据库构建蛋白质互作网络、Cytoscape 3.10筛选核心靶点、微生信平台进行基因本体和京都基因与基因组百科全书富集分析,最后用AutoDockTools 1.5.7进行核心靶点与有效成分验证。结果获得有效成分2个、交集靶点80个,核心靶点包括表皮生长因子受体(epidermal growth factor receptor,EGFR)等共18个;富集分析显示作用机制与磷脂酰肌醇3-激酶/蛋白激酶B信号通路等通路相关。分子对接结果表明EGFR和核心靶点所组成的对接体具有强烈的对接活性,最为稳定。结论LCZ696可能通过多靶点与多通路抑制IH治疗动静脉内瘘成熟障碍及狭窄,为LCZ696的进一步研究提供理论依据和潜在研究方向。Objective To explore the mechanisms of sacubitril valsartan sodium(LCZ696)for the treat-ment of delayed maturation and stenosis of arteriovenous fistula(AVF)through inhibition of intimal hyperpla-sia using network pharmacology and molecular docking methods.Methods The effective component of LCZ696 and its target molecules were obtained from the Chemical Book platform and SwissTarget prediction database.The targets of intimal hyperplasia were collected from GeneCards and Online Mendelian Inheri-tance in Man databases.Protein-protein interaction database was used to construct protein interaction net-work.Cytoscape 3.10 core target screening and microbioinformatics platform were used for gene ontology and Kyoto encyclopedia of genes and genomes enrichment analysis.Finally,AutoDockTools 1.5.7 was used to verify the core targets and active components.Results Two effective components and 80 intersection tar-gets were obtained,including 18 core targets such as epidermal growth factor receptor(EGFR).Enrichment analysis showed that phosphatidylinositol 3-kinase/protein kinase B signaling pathway related to the mecha-nism of action.Molecular docking showed that the docking body composed of EGFR and core target had strong docking activity and highest stability.Conclusion Sacubitril valsartan sodium may inhibit the intimal hyperplasia through multi-target and multi-pathway in the treatment of delayed AVF maturation and stenosis,providing theoretical basis and potential research pathways for further study of LCZ696.

关 键 词：沙库巴曲缬沙坦钠 网络药理学 内膜增生 动静脉内瘘 

分 类 号：R318.16[医药卫生—生物医学工程]