中国临床药学杂志2024，Vol.33Issue(12)：887-895,9.DOI:10.19577/j.1007-4406.2024.12.002
基于网络药理学和分子对接技术探讨替格瑞洛抗脓毒症心肌病的可能分子机制
Exploring the potential molecular mechanism of ticagrelor against sepsis-induced cardiomyopathy based on network pharmacology and molecular docking techniques
摘要
Abstract
AIM To explore the potential molecular mechanism of ticagrelor in the treatment of sepsis-induced cardiomyopathy(SIC)based on network pharmacology and molecular docking technology.METHODS Potential targets of ticagrelor were identified using the SwissTargetPrediction database.Subsequently,common targets against SIC were determined by obtaining disease targets from GeneCards,OMIM,and TTD databases and analyzing the overlap with a Venn diagram.The protein-protein interaction(PPI)network was obtained through STRING database.Cytoscape 3.9.1 was used to visualize and analyze the PPI network and 10 core targets were selected.Gene ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were conducted on core targets using the DAVID database to screen for significant signaling pathways in the treatment of SIC with ticagrelor.Finally,molecular docking was performed to verify the binding capacity between ticagrelor and core targets.RESULTS Through network pharmacological prediction,67 targets for ticagrelor,1 778 potential targets for septic cardiomyopathy,and 34 intersecting targets were selected.The 10 core targets in the PPI network included tumor necrosis factor(TNF),epidermal growth factor receptor(EGFR),heat shock protein 90 alpha family class A member 1(HSP90AA1),peroxisome proliferator-activated receptor gamma(PPARG),matrix metalloprotein 9(MMP9),NOD-like receptor family pyrin domain-containing 3(NLRP3),Janus kinase 2(JAK2),mitogen-activated protein kinase 1(MAPK1),mitogen-activated protein kinase 8(MAPK8),poly(ADP-ribose)polymerase 1(PARP1).GO and KEGG analysis of the hub targets found that ticagrelor mainly regulated necroptosis,interleukin-17(IL-17)signaling pathway,NOD-like receptor signaling pathway and other signaling pathways through hub targets(e.g.,TNF,HSP90AA1,NLRP3).Molecular docking results showed that ticagrelor could target the core targets TNF,HSP90AA1,MMP9,NLRP3,MAPK8,and PARP1.The lowest binding energy with NLRP3 was 7.16 kcal·mol-1.CONCLUSION This study provides preliminary verified that ticagrelor may act on targets such as TNF,HSP90AA1,MMP9,NLRP3,MAPK8,and PARP1,and regulate necroptosis,IL-17 signaling pathway,NOD-like receptor signaling pathway and other signaling pathways in SIC.关键词
替格瑞洛/脓毒症心肌病/网络药理学/分子对接Key words
ticagrelor/septic-induced cardiomyopathy/network pharmacology/molecular docking引用本文复制引用
徐利君,徐红燕,陈赛贞,叶佳丽,夏哲林,徐煜彬..基于网络药理学和分子对接技术探讨替格瑞洛抗脓毒症心肌病的可能分子机制[J].中国临床药学杂志,2024,33(12):887-895,9.基金项目
国家自然科学基金项目(编号82374008) （编号82374008）
浙江省卫生创新人才项目 （）
浙江省医药卫生科技厅项目(编号2024KY1823) （编号2024KY1823）
浙江省台州市科技局科技计划项目(编号21ywa33) （编号21ywa33）
台州市中心医院(台州学院附属医院)专项科研基金(编号2019KT033) （台州学院附属医院）
