通过5-HT/HTR7/Wnt/β-Catenin/NF-kB信号传递,抑制压力破坏了肠道平衡
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Updated: May 17, 2025

03:48
Restraint to Induce Stress in Mice and Rats
Published on: December 6, 2024
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Jiayu Yu1, Zixu Wang1, Yaoxing Chen1
1National Key Laboratory of Veterinary Public Health Security, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China.
International journal of molecular sciences
|May 14, 2025
概括
压力通过改变血清素 (5-HT) 水平,增加肠道透性和破坏肠道屏障,影响肠道健康. 阻断5-HT信号减轻肠道炎症,揭示了一个新的治疗点.
科学领域:
- 胃肠病学 胃肠病学
- 神经胃肠病学 神经胃肠病学
- 免疫学 免疫学 免疫学
背景情况:
- 压力会加剧炎症性肠病 (IBD) 和刺激性肠综合征 (IBS).
- 肠染色胺 (EC) 细胞和5-二三胺 (5-HT) 的异常与这些情况有关.
- 关联压力,5-HT和肠道屏障功能障碍的确切机制尚不清楚.
研究的目的:
- 为了阐明5-HT在压力诱导的肠损伤中的作用.
- 为了研究参与5-HT介导肠道炎症的信号通路.
- 确定与压力相关的胃肠道疾病的潜在治疗点.
主要方法:
- 控制压力被应用到小鼠来诱导压力.
- 测量了Tph1 (基酶1) 和5-HT的表达水平.
- 评估了肠道透性,紧结蛋白表达,杯状细胞计数和粘素分泌.
- 研究了5-HT受体HTR7,Wnt/β-catenin和NF-κB信号通路的作用.
- 使用了对5-HT信号的药理学阻断.
主要成果:
- 抑制压力增加了Tph1的表达和5-HT的产生.
- 高水平的5-HT导致肠道透性增加,紧结蛋白减少,杯状细胞减少,粘素分泌受损.
- 激活HTR7启动了Wnt/β-catenin信号传递,增加了EC细胞和5-HT分泌.
- Wnt/β-catenin激活也触发了NF-κB信号,促进了炎症性细胞因子的表达.
- 通过抑制Wnt/β-catenin激活,阻止5-HT信号传递改善了肠道炎症.
结论:
- 压力诱导的5-HT生产显著损害了肠道粘膜屏障.
- 5-HT/HTR7/Wnt/β-catenin/NF-κB轴是与压力相关的肠道炎症的一个关键途径.
- 针对5-HT信号提供了一个有前途的治疗策略,用于炎症性肠道疾病.
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