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HOPE和AMPK激活减少了灵长类牛排性肝移植中的反流损伤和代谢功能障碍
Tao Li1, Pengkang Chang2, Yimeng Wang3
1Department of Hepatobiliary Surgery, Institute of Advanced Surgical Technology and Engineering, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Scientific reports
|April 6, 2025
概括
低温氧化输液 (HOPE) 与AICAR相结合,有效地减少了供体肝脏的肥胖症,显著减轻了再输液损伤,并改善了灵长类动物模型中的肝功能. 这种方法提高了活体肝移植的移植质量.
科学领域:
- 移植免疫学 移植免疫学
- 器官的保存 器官的保存
- 代谢性肝病是一种代谢性肝病.
背景情况:
- 活肝移植,特别是对于儿科患者,越来越多地使用来自代谢相关脂肪肝病 (MAFLD) 的捐赠者的移植.
- 目前用于改善酸性移植质量的方法,如低温氧化 perfusion (HOPE),缺乏广泛的证据在灵长类动物模型快速降低酸和改善结果.
- 解决了解机械 perfusion 的有效性在降低肥胖症和重灌损伤在活体供体肝移植的差距至关重要.
研究的目的:
- 为了研究HOPE与AMPK激活剂AICAR结合的疗效,在活体肝移植的灵长类模型中改善脂肪性肝移植.
- 评估HOPE和HOPE+AICAR对降低肥胖症,减轻再输血损伤和改善肝功能标志物的影响.
主要方法:
- 在Cynomolgus子中建立了一个MAFLD模型,以模拟脂肪性肝移植.
- 左外叶肝经过静态冷保存 (2小时),希望 (2小时) 或希望+AICAR (2小时).
- 一种使用自主血液模拟移植后再输血的常温活体再输血模型 (IRM) 来评估移植活力和损伤.
主要成果:
- 与静态冷保存和单独使用HOPE相比,HOPE+AICAR显著减少了再注射损伤.
- HOPE+AICAR组的腺三酸盐 (ATP) 水平有所改善,氧化应激 (MDA,8-OHdG) 和炎症 (TNF-α,IL-6,TLR-4激活) 的标志物减少.
- HOPE+AICAR治疗导致肝脏甘油三和胆固醇水平降低,表明脂肪酸减少,p-AMPK水平增加.
结论:
- 将HOPE与AMPK激活剂 (如AICAR) 结合在一起,是一种有前途的策略,可以快速减少捐赠肝移植中的脂肪.
- 这种综合方法显著减轻了再输液损伤并改善了移植功能,为活体供体肝移植提供了潜在的进步.
- 这项研究提供了对机械 perfusion 技术的宝贵见解,以改善灵长类动物模型中稳态移植质量,解决了移植研究中的关键需求.
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