在胆固醇性肝病期间,肠道衰老的调节调节了屏障功能和肝病进展
Mar Moreno-Gonzalez1,2, Katherine Hampton1,3, Paula Ruiz1,2
1Gut Microbes and Health Institute Strategic Programme, Quadram Institute Bioscience, Norwich Research Park, Norwich, UK.
JHEP reports : innovation in hepatology
|September 24, 2024
概括
肠道细胞中的细胞衰老在胆固醇性肝病期间增加. 消除这些衰老细胞会使肝损伤恶化,这凸显了针对肠肝轴障碍的针对性,细胞特异性治疗的必要性.
科学领域:
- 胃肠病学和肝病学
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 胆固醇性肝病破坏了肠道屏障功能和微生物群,其机制尚不清楚.
- 衰老在胆管细胞 (有害) 和肝脏星状细胞 (抗纤维细胞) 中具有相反的作用.
研究的目的:
- 为了研究肠道衰老在胆固醇性肝病中的作用.
- 阐明胆固醇中肠肝轴干扰的机制.
- 评估针对肠道衰老的治疗潜力.
主要方法:
- 从患有原发性硬化性脑膜炎的患者和诱导胆固醇症的小鼠 (BDL,DDC饮食) 的肠道样本进行分析.
- 使用CaCo-2细胞和小鼠肠道器官的体外研究.
- 使用遗传 (p16-3MR小鼠) 和药理 (ABT-263) 方法消除衰老细胞.
- 用费克萨拉胺 (FXR激活剂) 和抗生素.
主要成果:
- 在人类和小鼠胆固醇性肝病中观察到肠上皮细胞 (IEC) 衰老的增加.
- IEC衰老与减少胆酸和增加脂多糖相关.
- 消除衰老细胞加剧了肝损伤,纤维化,IEC亡和肠道透性.
- IECs中的衰老与减少的增殖,但增加的肠干细胞激活有关.
结论:
- 在胆固醇性肝病期间,肠道衰老被激活.
- 消除老化的IECs对肠肝轴产生不利影响,恶化肝损伤.
- 针对衰老的细胞特异性向,而不是系统性消除,是胆固醇性肝病的潜在治疗策略.
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