保健医学研究与实践2025，Vol.22Issue(8)：36-44,9.DOI:10.11986/j.issn.1673-873X.2025.08.06
基于网络毒理学与分子动力学的双酚A衍生物致牙周炎的作用机制研究
Mechanism of bisphenol A derivatives inducing periodontitis based on network toxicology and molecular dynamics
摘要
Abstract
Objective To explore the mechanism of bisphenol A glycidyl methacrylate(Bis-GMA)derivatives in inducing pe-riodontitis based on network toxicology and molecular dynamics.Methods The Swiss Target Prediction database was used to screen potential targets for Bis-GMA.Periodontitis-related targets were obtained from GeneCards,Online Mendelian In-heritance in Man(OMIM),and Therapeutic Target Database(TTD)databases.The intersection of the predicted targets of Bis-GMA and periodontitis-related targets was used to construct the network.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed using DAVID,and a PPI network was constructed u-sing STRING.Core targets were identified using Cytoscape.Molecular docking was performed using AutoDock,and molec-ular dynamics simulations were carried out using GROM ACS.Results A total of 1,503 periodontitis-related disease targets were obtained by searching"periodontitis"in the database.Using Swiss Target Prediction,94 potential targets for Bis-GMA were identified.The intersection of the targets of Bis-GMA and periodontitis resulted in 29 targets,and a toxicology-target-disease network diagram was constructed.GO enrichment analysis showed that the Bis-GMA intervention targets for peri-odontitis mainly involve biological processes such as response to lipopolysaccharides,reaction to bacterial-derived molecules,and positive regulation of protein phosphorylation.KEGG enrichment analysis revealed that the main pathways involved in Bis-GMA's intervention in periodontitis are the regulation of transient receptor potential(TRP)channels by inflammatory mediators,the tumor necrosis factor(TNF)signaling pathway,and pathways related to lipid metabolism and atherosclero-sis.Molecular docking results indicated that Bis-GMA can stably bind to serine/threonine kinase 1(AKT1),phosphatidyli-nositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3CA),heat shock protein 90 alpha class A member 1(HSP90AA1),mammalian target of rapamycin(MTOR),matrix metalloproteinase-9(MMP9),non-receptor tyrosine ki-nase(SRC),phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta(PIK3CD),and mitogen-activated pro-tein kinase 8(MAPK8).Conclusion Bis-GMA may induce periodontitis by regulating multiple targets and pathways,medi-ating immune-inflammatory responses,apoptosis,and bone metabolism imbalance.关键词
牙周炎/网络毒理学/分子对接/分子动力学模拟/双酚A二缩水甘油醚二甲基丙烯酸酯Key words
Periodontitis/Network toxicology/Molecular docking/Molecular dynamics simulation/Bisphenol A glycidyl methacrylate分类
医药卫生引用本文复制引用
付浩轩,毛周洪,韩莉,张超,郑延延,彭嘉宽,唐婉容..基于网络毒理学与分子动力学的双酚A衍生物致牙周炎的作用机制研究[J].保健医学研究与实践,2025,22(8):36-44,9.基金项目
四川省科技厅重点研发项目(2022YFSY0043) （2022YFSY0043）
川北医学院博士科研启动基金项目(CBY24-QDA04). （CBY24-QDA04）
