全氟烷基化合物通过核受体信号通路介导的健康效应  

Health Impacts of Per- and Polyfluoroalkyl Substances Mediated through Nuclear Receptor Signaling Pathways

作　　者：王春凤 王建设 WANG Chunfeng;WANG Jianshe(School of Pharmacy,Yantai University,Yantai 264005,China)

机构地区：[1]烟台大学药学院,烟台264005

出　　处：《生态毒理学报》2025年第2期233-248,共16页Asian Journal of Ecotoxicology

基　　金：国家自然科学基金面上项目(21976178)。

摘　　要：全氟和多氟烷基化合物(PFAS)具有生殖和甲状腺等内分泌干扰效应、脂代谢毒性等。核受体(NR)信号是介导PFAS毒性效应的重要路径之一。我们认为PFAS能通过干扰NR信号途径的不同环节影响人类健康。在简要介绍PFAS和核受体的基础上,本文重点阐述PFAS对不同NR信号途径的作用方式、分子机制以及对生物体的不良效应,包括改变配体水平而间接改变NR活性,例如影响甲状腺激素和性激素的生成与转化,也包括对NR的直接激动或抑制效应,例如对甲状腺激素受体(TR)和过氧化物酶体增殖物激活受体(PPAR)的激动效应等。相应内容全面总结了PFAS通过何种途径、干扰了哪些NR信号途径和如何危害人类健康。因此,PFAS通过干扰NR配体的合成代谢和转运、干扰NR水平、激活或抑制NR、影响NR共作用因子等环节对人类健康造成威胁。但当前PFAS对某些NR干扰效应的具体作用环节尚不明确且很少涉及对NR翻译后修饰(PTM)的影响、对辅作用因子的选择性和靶基因表观遗传调控等方面。进一步完善和深入认识PFAS的NR干扰效应和作用机制,将为防控PFAS健康危害提供更多新见解和思路。Per-and polyfluoroalkyl substances(PFAS)exert endocrine-disrupting effects on reproductive and thyroid hormones,lipid metabolic toxicity,and other adverse effects.Nuclear receptor(NR)signaling is one of the key pathways mediating the toxic effects of PFAS.We believe that PFAS can affect human health by interfering with various components of the nuclear receptor signaling pathways.After a brief introduction to PFAS and NR,we focused on the mode of action,mechanism,and adverse outcomes of the NR signaling disturbance effect caused by PFAS.For example,PFAS indirectly modulates NR activity through alteration of ligand levels,such as affecting the production and metabolism of thyroid hormones and sex hormones.PFAS exert direct agonistic or antagonistic effects on NRs,such as the agonistic effects on the thyroid hormone receptor(TR)and peroxisome proliferator-activated receptor(PPAR).The corresponding content provides a comprehensive summary of how PFAS affect human health by interfering with various nuclear receptor(NR)signaling pathways.Specifically,PFAS poses a threat to human health by disrupting the synthesis,metabolism,and transport of NR ligands,altering NR levels,activating or inhibiting NRs,and affecting NR co-factors.However,currently,there are limitations in this field.The exact mode of action is unclear on some sort of NRs by PFAS.The influence on post-translational modification(PTMs)of NRs,the selectivity for co-factors,and the epigenetic regulation of target genes are also unclear.Thorough knowledge of NR signaling disturbance will provide new insights into the health hazards caused by PFAS.

关 键 词：全氟和多氟烷基化合物 核受体 毒性效应 内分泌干扰 作用途径 

分 类 号：X171.5[环境科学与工程—环境科学]