非酒精性脂肪性肝炎小鼠模型的构建

Establishment of Non-Alcoholic Steatohepatitis Mouse Model

摘要: 目的：构建特殊饲料饮食诱导的非酒精性脂肪性肝炎(nonalcoholic steatohepatitis, NASH)小鼠模型。方法：将40只8周龄的C57BL6/J雄性小鼠分成四组，分别予以高脂高果糖高胆固醇饮食(FFC)及对照饮食喂养4个月、6个月，期间每周称量小鼠体重，分别于喂养4个月和6个月取材，取动物血清和肝脏，进行血清学检测与肝组织病理学检测。结果：与对照组相比，FFC组体质量(P < 0.05)、肝湿重(P < 0.01)和肝体比(P < 0.01)均显著升高；FFC组脂肪变性明显比对照组严重(P < 0.001)；FFC组肝脏甘油三脂较对照显著升高(P < 0.001)，FFC组血清总胆固醇(TC)显著高于对照组(P < 0.001)，FFC组血清ALT (P < 0.05)、AST (P < 0.001)较对照显著升高。而且，FFC饮食喂养6个月比喂养4个月的小鼠具有更为严重的NASH疾病特征。结论：建立了不同严重程度的NASH小鼠模型，为研究NASH发病机制以及治疗等研究提供模型参考。

Abstract: Objective: To construct a mouse model of special diet-induced nonalcoholic steatohepatitis NASH. Methods: A total of 40 male C57BL6/J mice were divided into four groups, fed a high-fat, high-fructose and high-cholesterol diet (FFC) and a control diet for 4 months and 6 months, during which the body weight of mice was weighed weekly, and samples were collected at 4 months and 6 months respectively. Serum and liver of mice were collected for serological and histopathological detection. Results: Compared with the control group, the body mass (P < 0.05), liver wet weight (P < 0.01) and hepatic body ratio (P < 0.01) of the FFC group were significantly increased, the steatosis in the FFC group was significantly more serious than that in the control group (P < 0.001), the serum TC in the FFC group was significantly higher than that in the control group (P < 0.001), and the se-rum ALT (P < 0.05) and AST (P < 0.001) in the FFC group were significantly higher than those in the control group. Furthermore, mice fed the FFC diet for 6 months showed more severe features of NASH disease than those fed the FFC diet for 4 months. Conclusion: Mouse models of NASH with dif-ferent severity were established, which can provide a model reference for further study of the pathogenesis of NASH and the treatment.