洞察肠道屏障功能障碍和甲酸诱导肠道病变中的代谢变化
Clarisse Brossier1, François-Ludovic Sauvage1, Christel Valencia-Schmitt2
1INSERM, Univ. Limoges, Pharmacology & Transplantation, U1248, Limoges, France.
Basic & clinical pharmacology & toxicology
|February 2, 2026
概括
菌酸 (MPA) 损害了肠道屏障的完整性,并改变了细胞代谢,特别是在早期的肠道上皮细胞形成期间. 这些对屏障功能和核酸合成的影响,即使在MPA退出后也会持续下去.
科学领域:
- 胃肠病学 胃肠病学
- 药理学 药理学是指药理学的学科.
- 细胞生物学 细胞生物学
背景情况:
- 菌酸 (MPA) 是一种重要的免疫抑制剂.
- 胃肠道毒性限制了MPA的临床使用.
- 肠道细菌对MPA糖酸的代谢会增加局部MPA的暴露,可能会损害上皮质屏障功能和代谢.
研究的目的:
- 调查MPA对肠道屏障完整性的影响.
- 探索MPA对肠道上皮细胞代谢途径的影响.
主要方法:
- 卡科-2细胞暴露于MPA (10或100微米).
- 屏障功能的评估是使用跨体电阻 (TEER) 和黄 (LY) 透度.
- 细胞内代谢变化通过向LC-MS/MS代谢分析.
主要成果:
- 早期单层形成期间的MPA暴露降低了TEER和增加了LY透性,其影响持续到戒断后.
- 不同化的单层在屏障功能上没有显著变化.
- 代谢分析揭示了MPA暴露的细胞中明显的代谢概况,核酸合成途径发生了显著的改变.
结论:
- MPA可以破坏肠道上皮质屏障的完整性并改变细胞代谢,特别是在关键的早期发育阶段.
- 观察到的代谢干扰,特别是在核酸合成中,突出了MPA胃肠道毒性的潜在机制.
- 这些发现强调了除了免疫抑制作用外,考虑MPA对肠道健康的影响的重要性.
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