由DNA损伤引起的NORAD通过调节肺移植中的ferritinophagy来调节氧化压力
Jizhao Wang1, Ke Dong2, Yixing Li2
1Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China; Department of Pathology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
International journal of biological macromolecules
|January 29, 2026
概括
过度的自会使缺血-再输液损伤 (IRI) 恶化. 这项研究揭示了NORAD抑制费里丁,缓解肺IRI期间的氧化应激,并提供治疗潜力.
科学领域:
- 细胞生物学 细胞生物学
- 器官移植 器官移植
- 氧化压力研究研究 氧化压力研究
背景情况:
- 自在缺血-反损伤 (IRI) 中发挥着双重作用,对于减轻活性氧物种 (ROS) 至关重要,但过度时会加剧损伤.
- 肺移植失败是与IRI和器官损伤相关的重大临床挑战.
研究的目的:
- 探讨在IRI中自的矛盾作用,并确定调节氧化应激的机制.
- 探索ROS,DNA损伤和肺IRI中的ferritinophagy之间的关系.
- 评估NORAD作为抑制肺IRI中氧化应激的治疗标.
主要方法:
- 利用细胞,老鼠和患者衍生器官模型来研究在缺血期间ROS积累和自动态.
- 研究了诱导费里替诺法基及其与ROS激增和DNA损伤反应的联系.
- 采用小干扰RNA (siRNA) 向NORAD,通过脂质纳米粒子 (LNP) 和NORAD淘汰小鼠模型传递.
主要成果:
- 随着缺血时间的推移,ROS水平会增加,长期缺血后会出现激增,这与诱导的费里诺法基有关.
- 由ROS诱导的DNA损伤反应与ferritinophagy诱导相关.
- 通过调节FOXO1-NCOA4相互作用来激活ferritinophagy,NORAD被确定为激活ferritinophagy,其抑制在肺IRI模型中降低了氧化应激.
结论:
- 了解ROS诱导的DNA损伤,线粒和铁氨之间的相互作用对于解决IRI相关的细胞死亡至关重要.
- 通过抑制NCOA4介导的费里丁菌,NORAD成为抑制氧化应激和减轻肺部IRI的潜在治疗候选者.
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