摘要
甲状腺疾患是一种常见的内分泌系统疾病,其发展可能受到全氟及多氟烷基物质(PFAS)的影响.本研究采用不良结局途径(AOP)分析框架,探讨全氟辛烷磺酸(PFOS)和全氟辛酸(PFOA)对甲状腺功能的潜在影响机制.通过整合毒理学基因组学数据库(CTD)、GeneCards、DisGeNET、MalaCards、GO及KEGG的数据,建立了 PFOS/PFOA-基因-表型-甲状腺疾病的网络模型.以肿瘤坏死因子α(TNF-α)作为分子启动事件(MIE),本研究揭示了 PFOS和PFOA可通过升高TNF-α的水平,进而干扰甲状腺激素的代谢途径,诱发炎症反应、氧化应激及脂质与葡萄糖代谢的变化等关键事件(KE)发生,最终导致甲状腺功能障碍不良结局(AOP).这条AOP网络的发现为理解PFASs通过诱发炎症反应、氧化应激以及影响甲状腺激素、脂质和葡萄糖代谢从而对人类健康造成伤害提供了依据,对公共健康政策制定具有重要意义.
Abstract
Thyroid disorders are a common endocrine system disease,potentially influenced by perfluorinated and polyfluorinated substances(PFAS).This study employs the Adverse Outcome Pathway(AOP)framework to explore the potential mechanisms by which perfluorooctanesulfonic acid(PFOS)and perfluorooctanoic acid(PFOA)affect thyroid function.By integrating data from the Comparative Toxicogenomics Database(CTD),GeneCards,DisGeNET,MalaCards,Gene Ontology(GO),and the Kyoto Encyclopedia of Genes and Genomes(KEGG),a network model linking PFOS/PFOA,genes,phenotypes,and thyroid disease was established.Identifying tumor necrosis factor-alpha(TNF-α)as the Molecular Initiating Event(MIE),this research demonstrates how PFOS and PFOA can elevate TNF-α levels,thereby disrupting thyroid hormone metabolic pathways,and inducing inflammation,oxidative stress,and alterations in lipid and glucose metabolism—key events(KEs)that lead to the adverse outcome of thyroid dysfunction.These findings The discovery of this AOP network provides a basis for understanding how PFASs contribute to human health by inducing inflammatory responses,oxidative stress,and affecting thyroid hormone,lipid,and glucose metabolism,which are of significant relevance for public health policy formulation.
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