蒂米丁通过ATF3/p38通路在辐射诱导的肺损伤中诱导巨细胞M1极化
Hao Fan1, Xiangwei Ge2, Xin Zhou3
1Department of Oncology, The First Medical Centre, Chinese PLA General Hospital, Beijing 100000, China; No. 989 Joint Logistic Support Force Hospital, 471000 Luoyang, China.
Cellular immunology
|February 16, 2026
概括
辐射会提高提米丁,促进肺炎和巨细胞损伤. 针对这种代谢物或ATF3/p38通路提供了预防辐射诱导肺损伤的新策略.
科学领域:
- 免疫代谢过程中的免疫代谢.
- 辐射瘤学 辐射瘤学
- 肺部医学 肺部医学
背景情况:
- 辐射诱导肺损伤 (RILI) 是胸部放射治疗的一个主要并发症.
- 在RILI中,炎症和巨细胞功能障碍会导致膜损伤.
- 辐射后的代谢变化会影响巨细胞的两极分化,但触发因素尚不清楚.
研究的目的:
- 在RILI中确定M1巨分极的免疫代谢触发因素.
- 研究蒂米丁在辐射诱导的肺病理学中的作用.
- 探索针对已确定途径的治疗干预措施.
主要方法:
- 对暴露于辐射的肺组织和巨细胞的多组分析.
- 鼠类RILI模型与提米丁操纵 (饮食限制,AAV9-ATF3).
- 使用转录组和药物抑制剂的体外研究 (SB203580).
主要成果:
- 辐射后提升的胺激素驱动M1巨细胞的极化.
- 在小鼠中,饮食中限制蒂米丁或AAV9-ATF3输送减弱了RILI.
- 蒂米丁抑制了ATF3,并在被辐射的巨细胞中激活了MAPK/p38,形成了致病循环.
- 在体外,ATF3过度表达或p38抑制逆转了提米丁诱导的炎症.
结论:
- 蒂米丁-ATF3/p38轴是辐射诱导的肺免疫病理学的关键调节器.
- 代谢和转录干预措施对RILI治疗有希望.
- 向蒂米丁代谢或ATF3/p38通路可以补充辐射保护策略.
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