尼古丁通过诱导肠道失调和屏障功能障碍来加剧MASH
Fangfang Yi1, Jinyong Wang1, Yi Chen1
1Hepatology Diagnosis and Treatment Center, The First Affiliated Hospital of Wenzhou Medical University & Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver Diseases, Wenzhou, Zhejiang, China.
Communications biology
|December 5, 2025
概括
尼古丁通过破坏肠道微生物群和屏障功能,使代谢功能障碍相关的脂肪肝炎 (MASH) 恶化. 低氧诱导因子-1α (HIF-1α) 起着保护作用,益生菌可以提供治疗益处.
科学领域:
- 胃肠病学 胃肠病学
- 肝病学 肝病学是一种肝病学.
- 微生物学 微生物学
背景情况:
- 尼古丁在肠道中的积累加剧了与代谢功能障碍相关的脂肪肝炎 (MASH).
- 关联尼古丁暴露与MASH进展的确切机制尚不清楚.
- 肠道屏障功能障碍和微生物群的改变与MASH病变有关.
研究的目的:
- 在MASH小鼠模型中研究尼古丁对肠道微生物群组成和屏障完整性的影响.
- 阐明缺氧诱导因子-1α (HIF-1α) 在尼古丁诱导的MASH恶化中的作用.
- 探索益生菌补充剂在缓解尼古丁诱导的MASH中的治疗潜力.
主要方法:
- 使用一个暴露于尼古丁的MASH小鼠模型.
- 评估肠道微生物群的组成和屏障功能.
- 通过敲击实验调查了HIF-1α的作用,并分析了MEK/ERK信号通路.
- 评估了Lactobacillus rhamnosus GG超眠剂在缓解肝损伤方面的疗效.
主要成果:
- 尼古丁暴露诱导了显著的肠道微生物群失生症,并在MASH小鼠中增加了HIF-1α水平.
- HIF-1α倒置加剧了肠道屏障功能障碍,与抑制的MEK/ERK信号相关.
- 乳杆菌 rhamnosus GG 超眠体对肝损伤表现出保护作用,但在HIF-1α缺乏的小鼠中,这种保护作用被消除了.
结论:
- 尼古丁通过肠道微生物群的破坏和障碍功能障碍加剧MASH,与HIF-1α下调相关.
- 在尼古丁暴露的背景下,HIF-1α在维持肠道屏障完整性方面发挥着至关重要的作用.
- 益生菌补充剂代表了管理尼古丁诱导的MASH进展的潜在治疗策略.
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