基于网络毒理学与分子对接解析PBDEs致妊娠期SCH合并血脂异常、贫血的潜在毒性机制OA

Objective To explore the potential toxic mechanisms of polybrominated diphenyl ethers(PBDEs)-induced gesta-tional subclinical hypothyroidism(SCH)complicated with dyslipidemia and anemia based on network toxicology and molecu-lar docking,so as to provide a reference for clinical treatment.Methods By searching databases such as OMIM and Gene-Cards,disease-related genes for SCH,dyslipidemia,and anemia were collected,and potential targets for these three disea-ses were screened.R software(version 4.4.3)was used for Gene Ontology(GO)functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of the intersecting targets.A proteinprotein in-teraction(PPI)network was constructed based on the STRING database,and core targets were screened.Molecular docking validation was performed using AutoDock Vina 1.1.2.A regulatory interaction network of"thyroid hormone-lipid metabo-lism-pregnancy complications"was constructed to predict key signaling pathways involved in the study.Results TP53 was identified as the core target of PBDEs'effects on the"thyroid hormone-lipid metabolism-pregnancy complications"interac-tion network.Molecular docking results showed that the binding energy of the PBDEs-TP53 complex was-5.56 kcal/mol,indicating strong affinity.Conclusion PBDEs may disrupt the homeostasis of the"thyroid-lipid metabolism-anemia"inter-action network by targeting TP53 and activating inflammatory pathways,thereby exacerbating the risk of metabolicimmune imbalance during pregnancy.For pregnant women with gestational SCH complicated with dyslipidemia,reducing environ-mental exposure to PBDEs and implementing targeted interventions around inflammationrelated pathways may serve as novel prevention and treatment strategies to improve pregnancy outcomes in this population.