摘要
代谢相关脂肪性肝病(metabolic dysfunction-associated fatty liver disease,MAFLD)是一种与代谢紊乱紧密相关的全球性健康问题,其特征是肝脏内脂肪过度积聚,且可能进展为更严重的肝脏疾病,如代谢相关脂肪性肝炎(metabolic dysfunction-associated with steatohepatitis,MASH)、肝纤维化和肝细胞癌。随着MAFLD患病率的持续上升,其致病机制的研究及治疗方案的开发成为当前临床和基础医学领域的迫切需求。然而,目前MAFLD的治疗手段仍然有限,且尚未有经过验证的特效药物。本综述深入探讨了MAFLD体外模型的建立与药物筛选的研究进展,重点评述了二维细胞培养与三维类器官培养技术在模拟MAFLD病理状态中的各自优势与局限。而且,本文进一步分析了基于不同细胞来源的MAFLD模型在揭示药物作用机制、识别潜在治疗靶点以及提供临床前药物筛选平台方面的应用前景。本文旨在为未来MAFLD的临床治疗和药物开发提供新的思路和实验依据。
Metabolic dysfunction-associated fatty liver disease(MAFLD),a global health burden closely linked to metabolic disorders,is characterized by excessive intrahepatic lipid accumulation and potential progression to severe hepatic conditions,including metabolic dysfunction-associated steatohepatitis(MASH),fibrosis,and hepatocellular carcinoma.With the increasing prevalence of MAFLD,elucidating its pathogenic mechanisms and developing effective therapies have become urgent priorities in both clinical and basic medical research.However,current therapeutic options remain limited,with no validated disease-modifying agents available.This review comprehensively examines the advancements in establishing in vitro models of MAFLD and their application in drug discovery,with a critical evaluation of the comparative advantages and limitations of two-dimensional(2D)cell culture systems and three-dimensional(3D)organoid-based models in recapitulating MAFLD pathophysiology.Furthermore,this review analyzes the application prospects of MAFLD models derived from diverse cellular sources in deciphering drug mechanisms of action,identifying potential therapeutic targets,and providing preclinical drug screening platforms.Our objective is to provide novel insights and experimental evidence to guide future clinical interventions and pharmacological development for MAFLD.
作者
赫明达
张茜
高俊灵
王敏君
HE Mingda;ZHANG Qian;GAO Junling;WANG Minjun(The Sixth Student Team,College of Basic Medical Sciences,Naval Medical University/Second Military Medical University,Shanghai 200433,China;Department of Cell Biology,College of Basic Medical Sciences,Naval Medical University/Second Military Medical University,Shanghai 200433,China)
出处
《生命的化学》
2025年第7期1269-1277,共9页
Chemistry of Life
基金
国家自然科学基金项目(32070732)。
关键词
代谢相关脂肪性肝病
体外模型
干细胞
类器官
药物筛选
metabolic dysfunction-associated fatty liver disease
in vitro models
stem cells
organoids
drug screening
