由肠道微生物群衍生的醇通过准SCD1-MUFA轴来缓解辐射诱导的肠道损伤,以抑制ER压力
Xiaoya Jin1, Hetian Xue1, Xiaolin Shi1
1Institute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
International journal of biological sciences
|March 9, 2026
概括
铁醇是一种肠道代谢物,通过向SCD1.1,可以防止辐射引起的肠道损伤. 这种机制保持了肠道屏障的完整性,并减少了细胞死亡,为放射治疗并发症提供了新的治疗途径.
科学领域:
- 胃肠病学 胃肠病学
- 辐射瘤学 辐射瘤学
- 代谢学 代谢学 代谢学
背景情况:
- 辐射诱导性肠损伤 (RIII) 是放射治疗的严重并发症,治疗选择有限.
- 肠道衍生代谢物越来越多地被认为对宿主健康和疾病的作用.
研究的目的:
- 从肠道代谢产物中识别新的辐射保护剂.
- 为了阐明铁醇介导辐射保护的分子机制.
主要方法:
- 给致命辐射的小鼠注射泰洛索尔.
- 评估肠道组织学,上皮细胞死亡和炎症标志物.
- 生物化学试验以确定铁醇与醇-甲酸脱酶1 (SCD1) 的相互作用.
- 使用SCD1和单不和脂肪酸 (MUFA) 的抑制和补充研究.
主要成果:
- 铁醇显著改善了对照射小鼠的生存率,并保留了肠道粘膜屏障和状隐形结构.
- 发现醇直接结合和稳定SCD1,防止其降解.
- 这种稳定增加了MUFA水平,随后抑制了ER压力并减少了辐射诱导的细胞毒性.
- 抑制SCD1取消了铁的保护作用,而MUFA补充则在缺乏SCD1的细胞中恢复了辐射保护.
结论:
- 铁醇作为一种强大的辐射保护剂,可以防止胃肠道的辐射损伤.
- 该机制涉及铁醇诱导的SCD1稳定,导致MUFA的增加,抑制ER压力和缓解细胞毒性.
- 激活SCD1代表了管理RIII.III的有希望的治疗标.
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