非酒精性脂肪肝病小鼠模型的研究进展

Research Advances in Mice Models of Nonalcoholic Fatty Liver Disease

非酒精性脂肪肝病(Nonalcoholic fatty liver disease,NAFLD)发病率逐年升高,且尚无获批药物用于NAFLD的治疗,研究NAFLD的发病机制及研发有效的治疗药物迫在眉睫。小鼠具有繁殖迅速,饲养廉价,易于造模等特点,是NAFLD药物药效评价过程中最常用的动物模型。此外,NAFLD小鼠模型与NAFLD的研究密切相关,可模拟不同致病因素以及NAFLD每个阶段的病情发展,为阐明发病机制,找到潜在的治疗靶点提供不可或缺的指导,也是评估NAFLD治疗药物的关键。鉴于NAFLD治疗药物有更高安全性要求以及庞大和复杂的患病群体,构建能够更好地模拟人类NAFLD病理的小鼠模型仍然是该领域的研究前沿和热点问题。目前,尚缺乏对NAFLD小鼠模型较为全面系统的综述。围绕多种致病机制的NAFLD小鼠模型,即营养失调性模型、药物中毒性模型、基因缺陷模型、复合小鼠模型等不同病因的模型,对近年来已报道的NAFLD小鼠模型研究进展进行全面地总结综述,以期帮助研究者了解和选择最适合研究目标的NAFLD小鼠模型。

With the increasing of nonalcoholic fatty liver disease(NAFLD)and no approved drugs for the treatment of NAFLD,it is urgent to study the pathogenesis of NAFLD and develop effective therapeutic drugs.Due to their small size,lower cost,and short reproduction cycle,mice have been widely used to test the safety and efficacy for pharmaceutical development in NAFLD.The mice model of NAFLD is closely related to the research progress of NAFLD.It can simulate different pathogenic factors and the disease development of NAFLD stages.It provides indispensable guidance for elucidating the pathogenesis and finding potential therapeutic targets,and is also the key to the evaluation of NAFLD therapeutic drugs.There still remains a significant need for development of effective and highly safe drugs for increasing NAFLD population.The construction of mice models that can better simulate the pathology of human NAFLD,which is still a frontier and hot issue in this field.At present,there is a lack of comprehensive and systematic review of NAFLD mice models.This paper will comprehensively summarize and review the research progress of NAFLD mice models reported in recent years.And around a variety of pathogenic mice models of NAFLD,such as Dietary Models,Chemical Models,Genetic Models and Composite model,in order to help researchers know and select the more suitable mice model for the research goal.