奎尔素通过激活基碳化合物受体来保护性结肠炎的肠道屏障
Qiuzhu Wei1, Haixu Jiang2, Jia Zeng1
1School of Life Sciences, Beijing University of Chinese Medicine, Beijing, 102488, China.
概括
奎尔素通过激活基碳水化合物受体 (Ahr) 和调节中性粒细胞外陷 (NETs) 来加强性结肠炎的肠道屏障. 这种天然化合物减少了炎症和氧化应激,为肠道屏障修复提供了潜在的治疗策略.
科学领域:
- 胃肠道学和免疫学
- 药理学和自然产品的研究.
- 分子生物学分子生物学
背景情况:
- 性结肠炎 (UC) 涉及肠道屏障损伤,与酸受体 (Ahr) 激活显示治疗潜力.
- 中性细胞外细胞陷 (NETs) 参与UC病变发生,并受到活性氧物种 (ROS) 的影响.
- 奎尔塞丁 (QUE) 是一种天然化合物,激活Ahr以增强肠道屏障功能.
研究的目的:
- 调查 QUE 在 UC 中抑制 NET 的机制.
- 为了确定QUE如何在中性粒细胞中激活Ahr.
- 探索 QUE 对肠道屏障完整性和炎症的影响.
主要方法:
- 在体内研究中使用硫酸 (DSS) 诱导的UC小鼠模型.
- 进行了组织病理学染色 (H&E,PAS,Masson,alcian blue) 和细胞因子分析.
- 采用转录基因分析,西部斑点,IHC和IF测定;体外研究包括分子模拟和中性粒细胞共培.
主要成果:
- 奎尔丁的使用通过抑制NF-κB通路并上调Ahr/Arnt和Nqo1.1,显著预防了结肠炎症和肠道屏障破坏.
- 转录组和IHC分析证实了QUE的炎症和NET的减少.
- 在体外,QUE作为Ahr激动剂,激活Ahr转位并通过Arnt和Nqo1调节减少ROS产量.
结论:
- 在DSS诱导的大肠炎模型中,奎尔素通过调节NET形成,显著改善了肠道屏障功能.
- 奎尔赛丁激活了Ahr,并在中性粒细胞中调节了Arnt,从而调节了NET的形成.
- 通过针对Ahr和NETs,QUE显示出作为UC治疗剂的潜力.
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