与衰老相关的肝脏鼻状内皮细胞功能障碍加剧了与代谢功能障碍相关的稳态性肝病的进展
Qingqing Dai1,2,3, Quratul Ain1, Navodita Seth1
1Department of Internal Medicine IV (Gastroenterology, Hepatology, and Infectious Diseases), Jena University Hospital, Jena, Germany.
Aging cell
|February 6, 2025
概括
衰老会损害肝脏内皮细胞,恶化与代谢功能障碍相关的脂肪性肝病 (MASLD). 这项研究表明,衰老的LSEC会在患有MASLD的老年人中加剧肝损伤和纤维化.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 衰老研究研究 衰老研究
- 内皮细胞生物学 内皮细胞生物学
背景情况:
- 老龄化增加了对代谢功能障碍相关的脂肪性肝病 (MASLD) 的易感性.
- 肝脏的鼻状内皮细胞 (LSECs) 维持肝脏的平衡,但它们在MASLD中的与年龄相关的功能障碍尚不清楚.
- 研究老化中的LSEC功能障碍对于了解MASLD进展至关重要.
研究的目的:
- 调查与衰老相关的LSEC功能障碍对MASLD的影响.
- 评估老化的LSECs在肝细胞肥胖症和肝损伤中的作用.
- 评估Resveratrol在缓解LSEC衰老效应方面的治疗潜力.
主要方法:
- 自由脂肪酸处理的AML12肝细胞与年轻和老化的LSEC (TSEC细胞) 的共同培养.
- 在年轻和老年老鼠中诱导与代谢功能障碍相关的脂肪肝炎 (MASH),使用缺乏甲氨酸和胆的饮食.
- 在位肝输液用于血液动力学和内皮功能评估;分析人类肝脏组织.
主要成果:
- 衰老的LSECs取消了年轻的LSECs对肝细胞肥胖症的保护作用.
- 复星在老化的LSEC中部分恢复了NO介导的保护作用.
- 与年轻大鼠相比,老年MASH大鼠表现出恶化的肝损伤,肥胖症,纤维化和内皮功能障碍.
- 老年MASH患者表现出更严重的肝损伤和纤维化,并降低了eNOS和SIRT1水平.
结论:
- LSEC衰老会损害它们对肝细胞肥胖症的保护功能.
- 衰老加剧了MASH中的肝脏肥胖症,纤维化和LSEC功能障碍.
- 老年MASH患者的内皮功能障碍与更严重的肝损伤和纤维化有关.
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