迪布甲酸暴露会通过毛囊细胞灭通过NRF2/KEAP1/NF-κB通路诱导甲状腺毒性
Jieyi Wang1,2, Fangda Fu1, Yuying Chen3
1Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, China.
Annals of medicine
|March 17, 2026
概括
迪布甲酸盐 (DBP) 暴露会通过氧化应激和炎症导致甲状腺损伤. 这项研究揭示了DBP通过NRF2/KEAP1/NF-κB通路在甲状腺细胞中触发热,影响甲状腺功能.
科学领域:
- 毒理学 毒理学 毒理学
- 内分泌学 在内分泌学.
- 分子生物学分子生物学
背景情况:
- 双甲酸 (DBP) 是一种广泛使用的可塑剂,已知对多个器官有毒作用.
- 尽管DBP具有生物积累性,但DBP诱导的甲状腺毒性的机制仍然不太清楚.
研究的目的:
- 调查亚慢性DBP暴露是否导致甲状腺毒性.
- 阐明甲状腺毛囊细胞烧灭和NRF2/KEAP1/NF-κB通路在DBP诱导的甲状腺毒性中的作用.
主要方法:
- 雄性C57BL/6小鼠接受了8周的DBP (50或250毫克/公斤) 输入.
- 评估了系统性毒性,甲状腺功能,卵泡形态,亡,炎症和烧亡标志物.
- 评估了分子通路,包括NRF2/KEAP1和NF-κB信号传递.
主要成果:
- 暴露于DBP导致全身毒性,体重减轻,氧化应激标志物升高.
- 观察到甲状腺功能障碍,毛囊形态变化,亡,炎症和亡的增加 (上调的NLRP3,ASC,CASPASE-1,GSDMD).
- DBP抑制了NRF2/KEAP1抗氧化途径,并激活了NF-κB信号传递.
结论:
- DBP通过氧化应激,炎症和热致死诱导甲状腺毒性.
- 抑制NRF2/KEAP1通路和NF-κB激活是DBP诱导的甲状腺损伤的关键机制.
- 这些发现突出了长时间接触DBP的潜在健康风险.
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