长期暴露于低剂量的9 - 甲会通过破坏昼夜节律来诱导肝脂积累
Meitong Liu1, Yaqi Lu2, Hongjiang Zhou1
1College of Food Science and Engineering, Jilin University, Changchun, Jilin 130062, China.
Journal of hazardous materials
|July 8, 2025
概括
低剂量的9-甲 (9-ClPhe) 暴露导致肝脏脂肪的积累,通过通过酸受体 (AHR) 和BMAL1相互作用扰乱昼夜节律. 黑色素和AHR抑制剂可以减轻这些影响.
科学领域:
- 环境毒理学环境毒理学
- 分子生物学分子生物学
- 代谢障碍 代谢障碍 代谢障碍
背景情况:
- 9- (9-ClPhe) 是一种普遍存在的环境污染物.
- 长期,低剂量9-ClPhe的毒性尚未得到充分了解.
- 化多环芳 (ClPAHs) 具有潜在的健康风险.
研究的目的:
- 为了研究慢性低剂量9-ClPhe暴露对肝脏脂质积累的影响.
- 阐明9-ClPhe诱导的毒性背后的机制,重点关注昼夜节律的破坏.
- 探索对9-ClPhe毒性的潜在治疗干预措施.
主要方法:
- 在C57BL/6小鼠的90天连续暴露中,小鼠接受了低剂量的9-ClPhe.
- 对肝脂积累的组织病理学和生物化学分析.
- 评估BMAL1蛋白表达和昼夜节律标志物.
- 同免疫沉试验用于研究蛋白质相互作用.
- 使用PPARα激活剂 (WY14643),黑激素和AHR抑制剂 (CH223191) 的治疗.
主要成果:
- 低剂量的9-ClPhe暴露导致了显著的肝脂积累.
- 9-ClPhe降低了脑和肌肉ARnt样蛋白1 (BMAL1) 的表达,这是PPARα激活的关键因素.
- 黑素的使用恢复了BMAL1水平,并缓解了脂质积累.
- 通过9-ClPhe激活烯碳化合物受体 (AHR) 与BMAL1相互作用和昼夜干扰有关.
- 抑制AHR缓解了9-ClPhe诱导的脂质积累和昼夜干扰.
结论:
- 慢性低剂量9-ClPhe暴露通过昼夜节律的破坏促进肝脏脂质的积累.
- AHR-BMAL1相互作用是调解9-ClPhe毒性的关键机制.
- 针对昼夜节律通路,如黑激素,可能提供治疗潜力.
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