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暴露于DBP会通过激活AKT/NF-κB/NLRP3信号来诱导甲状腺炎症损伤
Lei Li1, Yunhui Xia2, Junhan Chen3
1Endocrinology Department, Yancheng No.1 People's Hospital, Affiliated Hospital of Medical School, Nanjing University, Yancheng, Jiangsu 224001, China.
Ecotoxicology and environmental safety
|August 25, 2023
概括
迪-n-丁甲酸盐 (DBP) 暴露会损害雄性大鼠甲状腺结构并引起炎症. 这通过其代谢物,单-n-丁甲酸盐 (MBP) 发生,激活炎症途径.
科学领域:
- 内分泌学 在内分泌学.
- 毒理学 毒理学 毒理学
- 分子生物学分子生物学
背景情况:
- 丁甲 (DBP) 已知对生殖和神经发育有毒.
- DBP对其他内分泌器官,特别是甲状腺的影响,仍然在很大程度上没有特征.
- 了解DBP对甲状腺功能的影响对于评估其更广泛的健康风险至关重要.
研究的目的:
- 为了研究DBP暴露对雄性大鼠甲状腺的影响.
- 阐明DBP诱导的甲状腺毒性的潜在分子机制.
- 评估炎症和特定信号通路在DBP内分泌干扰中的作用.
主要方法:
- 在两周内,雄性大鼠通过胃内注射给予不同剂量的DBP (0,50,250,500毫克/公斤/天).
- 在体外研究中使用了Nthy-ori 3-1甲状腺毛囊上皮细胞系,该细胞系使用了DBP的活性代谢物mono-n-butyl phthalate (MBP) 进行治疗.
- 分析包括对炎症标志物,细胞增殖和AKT/NF-κB/NLRP3等信号通路的激活的评估.
主要成果:
- 与对照组相比,DBP暴露导致甲状腺细胞增殖和炎症反应发生显著变化.
- 在体外,MBP通过激活AKT/NF-κB/NLRP3信号通路来调节关键的炎症性细胞因子 (TNF-α,IL-6,IL-1β).
- 佩利诺2 (Peli2) 被确定为促进NLRP3炎症酶激活的关键媒介.
结论:
- 暴露于DBP会导致雄性大鼠甲状腺的结构损伤和炎症.
- 活性代谢物MBP通过AKT/NF-κB/NLRP3途径和Peli2.2调解DBP的甲状腺毒性.
- 这项研究为DBP在甲状腺上的内分泌干扰潜力提供了新的见解.
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