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脂肪酸衍生的介质干细胞疗法调节线粒体功能,通过DDIT4/PGC-1α轴减轻乙氨基诱导的肝损伤

Yelei Cen^1,2, Caixia Xia^1,2,3, Shouhan Yao^1,2

¹State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, China-Singapore Belt and Road Joint Laboratory on Infection Research and Drug Development, National Medical Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, 79# Qingchun Road, 6A-5, Hangzhou, 310003, China.

Stem cell research & therapy

|November 23, 2025

概括

介质干细胞疗法显示,通过恢复线粒体功能来治疗乙氨基诱导的肝损伤 (AILI) 是有前途的. 这种方法激活了DDIT4/PGC-1α通路,为肝损伤提供了新的治疗策略.

科学领域:

肝病学肝病学是一种肝病学.
线粒体生物学线粒体生物学
干细胞疗法是一种干细胞疗法.

背景情况:

乙氨基过量是药物诱导性肝损伤 (AILI) 的主要原因,通常涉及线粒体功能障碍.
目前对AILI的治疗选择有限,需要新的治疗策略.
介质干细胞 (MSCs) 正在研究它们对调节线粒体功能的潜力.

研究的目的:

研究MSCs在治疗AILI中的治疗潜力.
阐明MSCs在AILI中调节线粒体功能的机制.
确定涉及MSC介导的防治AILI的关键分子通路.

主要方法:

建立了一个乙氨基诱导的肝损伤 (AILI) 鼠标模型.
脂肪酸衍生的MSCs (AMSCs) 被静脉注射给AILI小鼠.
分析了肝脏组织和血液,以检测肝脏缩和线粒体功能.
肝细胞特异性DNA损伤诱导转录4 (DDIT4) 淘汰赛小鼠被用于验证机制.

主要成果:

在AILI小鼠中,AMSC治疗显著降低了肝硬化,氧化应激和线粒体功能障碍.
在AILI中,DDIT4被确定为AMSC疗效的关键,在AILI患者肝脏样本中观察到它的上调.
通过DDIT4介导的PGC-1α上调,AMSCs促进了线粒体生物发生和线粒体衰变,恢复了线粒体功能.

结论:

基于MSC的细胞治疗有可能通过调节线粒体功能来治疗AILI.
在AILI中,DDIT4/PGC-1α通路是肝脏线粒体保护的关键媒介.
这项研究为AILI的干细胞治疗提供了新的机制理解,并确定了潜在的临床点.

关键词:

乙氨基是一种严重的肝衰竭是急性肝衰竭.在DDIT4中,DDIT4是DDIT4.介质细胞干细胞介质细胞干细胞线粒体中的线粒体.

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Mesenchymal Stem Cells

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