Abstract: Objective To explore the mechanisms of sacubitril valsartan sodium (LCZ696) for the treatment of delayed maturation and stenosis of arteriovenous fistula (AVF) through inhibition of intimal hyperplasia 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 Inheritance in Man databases. Protein-protein interaction database was used to construct protein interaction network. 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 targets 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 mechanism 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.

Key words: Sacubitril valsartan sodium, Network pharmacology, Intimal hyperplasia, Arteriovenous fistula