临床前大小鼠MASH模型研究进展及在药物测试中的应用

摘要/Abstract

摘要： 临床前代谢功能障碍相关脂肪性肝炎(MASH)模型是研究病理,验证新疗法、新靶点或者病理标志物的关键工具。目前,尚无模型能够复制人类MASH的所有表型和组织学特征,因而实验前需要了解各种模型的优缺点,根据药物的靶点选择适配的模型。本文综述4类临床前MASH模型:(1)基因编辑模型:将靶基因人源化和敲除等;(2)饮食诱导模型:模仿病因学或者自然史,采用高脂高糖高胆固醇饲料或营养缺乏饲料;(3)化学(毒素)诱导模型:化学药物诱导实验动物,使其表现出类似于人类MASH疾病的病理特征;(4)人源化肝脏小鼠模型。同时,本文对利用上述模型测试过的药物进行小结。由于肝脏代谢在物种间存在不同程度差异,因而“人源肝细胞模型”或“肝脏和免疫双人源化的动物模型”是药物测试的重要补充,也是未来最理想的两类体外和体内模型。

杨炜峰, 刘树君, 刘俊浩, 苗振川, 尹明. 临床前大小鼠MASH模型研究进展及在药物测试中的应用[J]. 肝脏, 2025, 30(6): 764-768.

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