盘子中的代谢功能障碍相关的脂肪性肝病:人类精确切割肝脏切片作为药物查和干预的平台
Mei Li1, Frederik T Larsen2, Marius C van den Heuvel3
1Department of Pharmaceutical Technology and Biopharmacy, Groningen Research Institute of Pharmacy, University of Groningen, 9713 AV Groningen, The Netherlands.
Nutrients
|March 13, 2024
概括
人类肝脏切片的延长化模型代谢功能障碍相关的脂肪性肝病 (MASLD) 进展,包括脂肪症,炎症和纤维化. 这为开发MASLD疗法提供了一个新的临床前工具.
科学领域:
- 肝病学和代谢研究.
- 临床前疾病建模模型
背景情况:
- 与代谢功能障碍相关的脂肪性肝病 (MASLD) 是一个严重的健康问题,治疗选择有限.
- 可靠的临床前模型对于推动MASLD研究和治疗开发至关重要.
- 现有的人类精密切切肝切片 (PCLS) 模型主要集中在MASLD的启动上,缺乏全面的进展研究.
研究的目的:
- 延长人类PCLS的潜伏期,以调查MASLD的进展.
- 建立一个强大的外体模型来评估潜在的MASLD治疗干预.
主要方法:
- 健康的人类PCLS被培养长达96小时.
- 一种含有高糖,高胰岛素和高脂肪酸的特殊介质被用来诱导MASLD.
- 分析包括通过RNA测序评估脂肪,炎症,纤维化标志物和基因表达.
主要成果:
- 患有PCLS的人患有肝硬化症,脂肪代谢的变化取决于时间 (吸收/储存增加,氧化/分泌减少).
- 诱导MASLD导致肝炎 (增加的促炎基因和细胞因子) 和纤维化 (增加的促原1a1和TIMP1).
- RNA测序揭示了TNFα和TGFβ信号通路的持续激活,这与炎症和纤维化有关.
结论:
- 人类PCLSs的长时间化有效地模拟了MASLD的进展,包括肥胖症,炎症和纤维化.
- 这种扩展的PCLS模型为识别和测试新的MASLD治疗策略提供了一个有价值的平台.
- 这项研究强调了PCLSs对于肝脏疾病的综合性ex vivo调查的有用性.
相关概念视频
01:26Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow
382
Chronic liver disease significantly impacts drug metabolism due to alterations in hepatic blood flow and enzyme accessibility. This disruption affects the body's pharmacokinetics—the movement and processing of drugs within the system. Key enzymes crucial for metabolizing medications become less accessible, changing how drugs are processed and utilized. Furthermore, liver disease influences the synthesis of plasma proteins, such as albumin and globulins, which play critical roles in drug...
382
01:22Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test
271
In clinical practice, the direct measurement of hepatic blood flow to evaluate liver function presents significant challenges due to the intricate and specialized nature of the necessary techniques. Consequently, healthcare professionals often rely on empirical estimates derived from thorough patient examinations and liver function tests to gauge liver health. Among the tools at their disposal, the Child–Pugh and MELD scoring systems stand out for their ability to categorize and assess...
271