格雷林通过促进miR-143/ATG2B介导的自,改善了败血症中小肠道屏障损伤
Jingquan Liu1, Kai Shi2, Hanhui Cai1
1Emergency and Critical Care Center, Intensive Care Unit, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China.
PloS one
|August 7, 2025
概括
格林 (GHS) 通过调节miR-143和ATG2B介导的自,改善了败血症中的肠壁损伤. 这表明miR-143/ATG2B作为败血症诱导的肠道损伤的治疗点.
科学领域:
- 胃肠病学 胃肠病学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 肠道屏障损伤是败血症发展的关键因素.
- 众所周知,格林素 (GHS) 可以恢复肠道屏障功能.
- 对于GHS在败血症中保护肠道屏障的确切机制尚不完全理解.
研究的目的:
- 阐明格林在败血症中对肠道屏障损伤的保护作用背后的机制.
- 研究miR-143和ATG2B在GHS介导的自和肠壁修复中的作用.
- 探索miR-143/ATG2B途径作为败血症治疗点的潜力.
主要方法:
- 已建立的通过结和刺穿的败血症的老鼠模型和由脂多糖诱导的IEC-6细胞模型.
- 在体模型中施用GHS和操纵miR-143表达.
- 评估了肠道病理损伤,D-乳酸水平,紧结蛋白表达和自标记 (自细胞/自解细胞数,贝克林-1,p62,LC3I/LC3II).
- 在IEC-6细胞中确定了miR-143和ATG2B之间的直接相互作用.
主要成果:
- GHS治疗显著减轻了肠道病理性损伤,并降低了败血症大鼠的D-乳酸水平.
- GHS增加了紧结蛋白表达,ATG2B,Beclin-1和LC3I/LC3II水平,同时降低了miR-143和p62水平.
- 过度表达miR-143逆转了GHS的保护作用,表明其抑制作用.
- 细胞实验证实GHS增强了细胞活力和自溶酶体的形成,结果与有关miR-143,ATG2B和自标志物的体内结果一致.
- ATG2B被确定为miR-143.3的直接目标.
结论:
- 格林 (GHS) 通过miR-143/ATG2B介导的自途径改善了败血症引起的肠壁损伤.
- 在败血症期间,miR-143/ATG2B轴在调节自和肠壁完整性方面发挥着至关重要的作用.
- 向miR-143/ATG2B通路代表了与败血症相关的肠道功能障碍的有希望的治疗策略.
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