血管素抑制同时减轻了与酒精相关的肝脏和肌肉损伤
Zhaodi Che1, Mingxiang Cai2, Xiaowu Dong3
1Department of Anesthesiology and Clinical Research Institute, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China.
Metabolism: clinical and experimental
|May 1, 2025
概括
肝激素血管激素 (AGT) 通过激活氨酸-血管激素系统 (RAS) 来驱动与酒精相关的肝病 (ALD) 和酒精肌病 (AM). 针对这一途径为这两种疾病提供了一种新的治疗策略.
科学领域:
- 内分泌学 在内分泌学.
- 肝病学 肝病学是一种肝病学.
- 肌肉生理学 肌肉生理学
背景情况:
- 与酒精相关的肝病 (ALD) 涉及到复杂的器官通信通路,这些通路尚未完全理解.
- 肝激素,特别是血管激素 (AGT) 和氨酸-血管激素系统 (RAS) 在ALD病变发生中的作用是一个正在积极研究的领域.
研究的目的:
- 研究ALD中AGT和RAS的内分泌功能.
- 阐明AGT在饮酒背景下影响肝脏和骨肌肉的机制.
主要方法:
- 在老鼠的慢性狂饮乙醇消费模型中.
- 在Agt (AGTΔHep) 和AGTflox/flox (AGTf/f) 小鼠的肝细胞特异性淘汰中.
- 对酒精性肌肉病 (AM) 现象型的分析,包括肌肉质量,氧化应激和线粒体功能.
- 药理上抑制了AGT,雷宁,血管酶转化酶和AGTR1.1.
- 在肝细胞和肌细胞中,Agtr1和Mas1的遗传淘汰.
- 对Ang{1-7) -MAS1轴的评估.
主要成果:
- 慢性乙醇摄入增加了肝脏AGT的产生,并激活了RAS.
- 肝细胞中的AGT淘汰会显著降低ALD的严重程度.
- 在骨肌肉中,AGT缺乏改善了AM相关的表型.
- AGT-AGTR1轴向肝细胞和肌细胞传递有害信号.
- 抑制AGT,雷宁,ACE或AGTR1减弱的肝脏和肌肉损伤.
- 1-7-MAS1轴的激活改善了酒精损伤.
- 马斯1倒闭加剧了肝脏和肌肉损伤.
结论:
- 肝素AGT通过RAS-AGTR1轴促进ALD和AM.
- 在ALD和AM中,AGT抑制了保护性Ang{1-7) -MAS1轴.
- 准AGT-RAS通路为ALD和AM同时治疗提供了潜在的治疗策略.
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