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通过使用人类肝脏球状共培养来研究亲肠营养诱导的肝毒性

Milos Mihajlovic¹, Sybren De Boever¹, Andrés Tabernilla¹

¹Department of Pharmaceutical and Pharmacological Sciences, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090, Brussels, Belgium.

Archives of toxicology

|May 13, 2024

概括

全腹腔营养 (TPN) 可以导致肝损伤,称为肠衰竭相关肝病 (IFALD). 这项研究揭示了TPN改变肝细胞基因表达,并触发关键的损伤途径,包括肥胖症.

科学领域:

肝病学肝病学是一种肝病学.
分子生物学分子生物学
营养科学营养科学

背景情况:

胃肠道营养 (PN),特别是全体胃肠道营养 (TPN),对于胃肠道功能障碍患者至关重要.
TPN可能导致显著的不良影响,特别是TPN相关的肝损伤 (IFALD),影响高达90%的接受者.
在IFALD背后的分子机制仍然不太清楚.

研究的目的:

为了阐明驱动IFALD的分子机制.
研究TPN及其成分对肝损伤途径的影响.
分析暴露于TPN的肝细胞中的转录组变化.

主要方法:

使用的人类肝脏球状共同培养物,用TPN混合物处理.
进行RNA测序以分析转录组概况.
评估的肝损伤关键事件:线粒体功能障碍,ER压力,氧化压力,亡和脂肪.

主要成果:

长时间的TPN暴露显著改变了肝球体的转录组.
TPN影响了多个代谢和信号通路,与肝损伤有关.
TPN,特别是脂质乳液,诱导了所有测量的损伤事件,包括脂肪.

结论:

TPN显著影响肝细胞的分子通路,有助于IFALD.
了解这些机制对于减轻与TPN相关的肝损伤至关重要.
脂质乳液是驱动TPN诱导的肝病理的一个关键组成部分.

关键词:

与肠道衰竭相关的肝病.肝脏球状共同培养肝脏毒性肝脏毒性有关RNA测序的RNA测序总的亲肠道营养

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