亚特拉提烯胺-I通过准S100A9/AMPK/mTOR信号通路来恢复肠道屏障功能
Chen Chen1,2,3, Bingjie Sun1, Keming Chen1
1Nanjing University of Chinese Medicine, Nanjing, China.
Frontiers in pharmacology
|April 8, 2025
概括
阿特拉提利诺利德-I (AT-1) 通过降低S100A9和调节AMPK/mTOR通路来保护性结肠炎中的肠壁. 这种化合物为这种炎症性肠病提供了潜在的治疗益处.
科学领域:
- 胃肠病学和肝病学
- 药理学和制药科学 药理学和制药科学
- 分子生物学分子生物学
背景情况:
- 肠上皮质屏障功能受损是性结肠炎 (UC) 发病的一个关键因素.
- 阿特拉提利诺利德-I (AT-1),是来自*Atractylodes macrocephala* Koidz.的化合物,在缓解大肠炎方面显示出有前途.
- 了解AT-1对肠道屏障完整性的机制对于UC治疗开发至关重要.
研究的目的:
- 研究AT-1在性结肠炎中对肠上皮质屏障功能的保护作用.
- 阐明AT-1发挥治疗作用的潜在分子机制.
主要方法:
- 在小鼠中建立了急性结肠炎模型,并进行了转录组分析.
- 使用过度表达等离子体和重组蛋白质的实验室细胞模型.
- 研究了S100A9,紧结蛋白和AMPK/mTOR信号通路的作用.
主要成果:
- AT-1改善了DSS引起的急性性结肠炎,并保护了肠道屏障.
- 转录基因分析发现S100A8和S100A9被AT-1显著调节.
- 在S100A9中介的紧结蛋白表达;AT-1减少中性粒细胞激活和S100A9释放.
- 通过AMPK/mTOR通路调节AT-1紧结蛋白,独立于S100A9.9诱导的细胞内Ca2+变化.
结论:
- 通过增强肠道屏障功能,AT-1显示出对DSS诱导的性结肠炎的显著保护作用.
- 该机制涉及调节S100A9介导作用和调节AMPK/mTOR信号通路.
- AT-1 提出了性结肠炎治疗的潜在治疗策略.
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