过度暴露于超加工食品会通过巨细胞铁灭症加剧性结肠炎
Xiaoqi Pang1, Jing Yan2, Xinrui Lv1
1Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, National Key Clinical Specialty, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin 300052, China.
Environment international
|August 1, 2025
概括
超加工食品含有7-托醇 (KS),通过破坏抗氧化剂防御和触发巨细胞铁亡,使性结肠炎 (UC) 恶化. 这突显出一种新的饮食与UC病变的联系.
科学领域:
- 胃肠道学和营养学
- 分子生物学和免疫学 分子生物学和免疫学
背景情况:
- 性结肠炎 (UC) 是一种慢性炎症性疾病,其全球流行率越来越高.
- 环境因素,包括含有氧化植物的超加工食品 (UPF),都与UC有关.
- 植物氧化产物,如7-基 (KS) 在肠道炎症中的特定作用基本上是未知的.
研究的目的:
- 调查UPF中主要的植物氧化物7-托醇 (KS) 在性结肠炎 (UC) 病变发生过程中的作用.
- 阐明KS影响肠道炎症和巨细胞功能的分子机制.
主要方法:
- 临床饮食分析,将KS摄入量与UC严重程度相关联 (梅奥得分).
- 牛硫酸 (DSS) 诱导的大肠炎的小鼠模型,以评估KS的影响.
- 使用RAW264.7细胞进行体外研究,以研究KS对ALKBH5-GCLM通路和铁亡的影响.
- 对临床UC标本进行免疫光分析,以验证KS-ALKBH5-GCLM轴.
主要成果:
- 在UC患者中,较高的KS摄入量与梅奥得分增加相关.
- 在小鼠中,KS加剧了DSS诱导的大肠炎,并通过抑制ALKBH5-GCLM轴,削弱了巨细胞的抗氧化防御.
- KS抑制了ALKBH5的核转移,降低了GCLM的调节,谷氨生物合成,并促进了巨细胞铁亡.
- ALKBH5过度表达挽救了GCLM表达和减轻了铁;在临床UC样本中证实了KS介导的这一轴的抑制.
结论:
- 来自超加工食品的饮食7-二 (KS) 是性结肠炎 (UC) 病原体的新型环境驱动因素.
- 通过KS-ALKBH5-GCLM信号通路诱导巨细胞铁亡,KS促进UC.
- KS-ALKBH5-GCLM-ferroptosis轴代表了UC干预的潜在治疗目标.
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