通过Scd1介导的代谢变化参与了肝脏对低剂量巴巴维的反应
Pan Shen1, Zhi-Jie Bai1, Lei Zhou1
1Department of Pharmaceutical Sciences, Beijing Institute of Radiation Medicine, Beijing, 100850, China.
Journal of pharmaceutical analysis
|August 14, 2023
概括
来自中国传统医学的巴瓦 (BV) 在明显受伤之前会导致早期的肝细胞变化,包括肥胖症. 乙基CoA脱酶1 (Scd1) 被确定为预测这种早期肝毒性的关键分子.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 毒理学 毒理学 毒理学
- 分子生物学分子生物学
背景情况:
- 传统中医药中的生物活性成分可能会导致延迟发病的肝毒性.
- 药物诱导性肝损伤 (DILI) 的早期检测具有挑战性,因为无症状阶段缺乏生物标志物.
- 众所周知,Fructus Psoraleae的成分巴瓦 (BV) 诱导肝脏损伤,但其早期细胞反应仍然不清楚.
研究的目的:
- 在没有观察到副作用的水平上研究肝细胞对巴瓦 (BV) 的细胞和分子反应.
- 确定BV诱导的肝毒性早期指标和潜在机制.
- 探索脂质代谢和特定基因在BV诱导的肝损伤无症状阶段的作用.
主要方法:
- 鼠被用BV治疗了7天,以评估生化和组织学变化.
- 单细胞RNA测序被用来对肝细胞和非帕伦基马细胞中的基因表达进行分析.
- 分析了参与脂质代谢和细胞反应的关键基因和途径.
主要成果:
- 在没有明显生化异常的小鼠中,使用无毒剂量的BV治疗诱导了微妙的肝肥胖症.
- 单细胞分析揭示了不同的肝细胞子集,其中"hepa3"亚型显示了脂质代谢的显著变化.
- 观察到醇-CoA脱酶1 (Scd1) 的表达增加,促进单不和脂肪酸 (MUFA) 合成,并可能启动铁亡.
- 通过Srebf1和Hnf4a等转录因子以及利基细胞信号的调节,与这些分子事件有关.
结论:
- 在检测到肝损伤之前,BV暴露会在特定的肝细胞子集中引发早期,微妙的脂质代谢变化.
- 乙基CoA脱酶1 (Scd1) 在BV诱导的乙酸和铁酸开始中起着至关重要的作用.
- Scd1 作为一种潜在的早期预测生物标志物,用于巴瓦诱导的肝毒性.
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