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PUFAs通过加剧肠道上皮脂过氧化,增加了与克罗恩病相关的AIEC诱导肠炎的燃料
Weiwei Wen1,2, Yihan Xu2, Wenwei Qian1,2
1Department of General Surgery, Jinling Hospital, Medical School of Southeast University, Nanjing, China.
粘附性侵入性大肠杆菌 (AIEC) 和多不和脂肪酸 (PUFA) 通过促进肠细胞中的脂质过氧化和铁化,加剧克罗恩病. 抑制铁亡可以缓解AIEC诱导的肠炎.
科学领域:
- 胃肠病学 胃肠病学
- 微生物学 微生物学
- 细胞生物学 细胞生物学
背景情况:
- 克罗恩氏病 (CD) 的发病包括肠上皮细胞 (IEC) 脂质过氧化 (LPO),可能被多不和脂肪酸 (PUFA) 加剧.
- 肠道失生症,特别是固侵入性大肠杆菌 (AIEC) 的增加,与CD有关,但其在LPO和铁亡中的作用尚不清楚.
研究的目的:
- 调查AIEC对LPO和IEC中的铁病的影响.
- 为了确定PUFAs是否会加剧AIEC引起的肠炎症.
- 探索针对铁亡的治疗策略.
主要方法:
- 对CD患者的LPO标记物和与铁死相关的蛋白质 (GPX4,FTH) 的IEC分析.
- 在体外感染IECs与AIEC,有或没有PUFA补充剂,评估LPO和ferroptosis.
- 使用DSS和抗生素尾酒小鼠模型进行体内研究,以评估PUFA诱导肠炎的AIEC,有或没有铁灭抑制剂治疗.
主要成果:
- 在CD患者中AIEC殖民与减少GPX4/FTH和增加LPO (4-HNE) 相关联.
- 在体外的AIEC感染诱导了IEC中的LPO和ferroptosis,PUFAs (AA,DHA) 恶化了这种情况.
- 保护IECs的GPX4过度表达;铁素-1治疗改善了小鼠的AIEC诱导肠炎.
结论:
- AIEC促进IEC中的LPO和ferroptosis,有助于CD的肠道炎症.
- 补充PUFA会加剧AIEC诱导的LPO和铁亡.
- 向铁亡可能是AIEC驱动的肠道炎症的治疗方法.
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