暴露于triclosan会通过IL-1β-NF-κB-Fxr信号通路引起胆酸代谢异常
Jing Liu1, Fang Xu2, Mingzhu Guo2
1College of Eco-Environmental Engineering, Guizhou Minzu University, Guiyang 550025, China; State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China.
Ecotoxicology and environmental safety
|September 11, 2024
概括
特里克洛桑 (TCS) 通过抑制Fxr来破坏胆酸循环,导致肝脏受损. 这一途径涉及热致死,IL-1β和NF-κB,这表明Fxr是治疗点.
科学领域:
- 毒理学 毒理学 毒理学
- 分子生物学分子生物学
- 肝病学 肝病学是一种肝病学.
背景情况:
- 特里克洛桑 (TCS) 是一种广泛使用的抗菌剂,具有已知的健康风险.
- TCS 破坏胆酸 (BA) 肠肝循环,但毒性机制尚不清楚.
- 由于其广泛使用,了解TCS毒性至关重要.
研究的目的:
- 阐明TCS在胆酸循环中的毒性机制.
- 为了研究TCS诱导的肝损伤所涉及的分子通路.
- 确定TCS相关疾病的潜在治疗点.
主要方法:
- 在体内建立了一个为期8周的TCS暴露模型.
- 分析了编程细胞死亡,炎症和BA在肝脏中的积累.
- 研究了与BA合成和运输相关的基因表达.
- 探索了Fxr,热,IL-1β和NF-κB信号通路的作用.
主要成果:
- 暴露于TCS诱导了细胞死亡,炎症和过度的BA在肝脏中的积累.
- 参与BA合成和运输的TCS失调基因.
- 由TCS诱导的Fxr抑制被确定为BA障碍的关键因素.
- 通过NF-κB信号传递,Pyroptosis和IL-1β调解了Fxr的减少.
结论:
- 由TCS诱导的胆酸乱是由Fxr抑制引起的.
- IL-1β-NF-κB信号通路通过TCS调解Fxr抑制.
- Fxr是TCS引起的胆酸代谢异常的潜在治疗标.
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