主体ALDH2缺乏症通过肠肝轴加剧非酒精性脂肪肝炎
Zhan-Ming Li1, Chao-Yue Kong1, Yu-Qin Mao1
1Center for traditional Chinese medicine and gut microbiota, Minhang Hospital, Fudan University, 201199 Shanghai, China; Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, 201199 Shanghai, China.
Pharmacological research
|September 1, 2023
概括
线粒体脱酶 (ALDH2) 缺乏会通过破坏肠道微生物群和胆汁酸来加剧非酒精性脂肪肝炎 (NASH). 补充乳酸菌或石灰酸 (LCA) 显示了NASH的治疗潜力.
科学领域:
- 肝病学 肝病学是一种肝病学.
- 微生物学 微生物学
- 代谢性疾病 代谢性疾病
背景情况:
- 非酒精性脂肪肝炎 (NASH) 是导致肝功能障碍的主要原因.
- 线粒体化物脱酶 (ALDH2) 与脂肪肝疾病有关,但其在NASH病变发生过程中的作用尚不清楚.
研究的目的:
- 调查ALDH2在NASH发展中的作用,并阐明潜在机制.
- 检查ALDH2缺乏对肠道微生物群和NASH中的胆酸代谢的影响.
主要方法:
- 给ALDH2淘汰和野生类型小鼠食甲素胆缺乏 (MCD) 饮食以诱导纳氏病.
- 分析便,血清和肝脏样本,包括肠道微生物群组成和胆酸概况.
- 干预研究涉及微生物移植,Lactobacillus gavage和石化酸 (LCA) 补充.
主要成果:
- 在MCD饮食下,ALDH2淘汰赛小鼠表现出恶化的肝炎,脂肪积累和肠道损伤.
- 缺少ALDH2导致肠道微生物群失调,其特点是乳酸菌的丰度减少.
- 在ALDH2淘汰小鼠中观察到胆汁盐化酶活性降低和特定胆汁酸 (LCA),以及下调的FXR-FGF15信号传递.
- 乳酸菌补充剂和LCA的使用改善了ALDH2缺乏小鼠中的NASH严重程度.
结论:
- 通过维持肠道微生物群平衡和调节胆酸代谢,ALDH2在NASH中起着保护作用.
- 失生症和改变的胆酸概况,特别是减少的LCA,有助于NASH在ALDH2缺乏症的进展.
- 向肠道微生物群 (乳酸菌) 和胆汁酸 (LCA) 是与ALDH2缺乏相关的NASH的潜在治疗策略.
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