果糖诱导非酒精性脂肪性肝病小鼠动物模型的构建和评价

目的建立果糖诱导的非酒精性脂肪肝病(NAFLD)小鼠模型并评价其特征。方法给予C57BL/6小鼠30%(w/v)果糖水饲养8周,正常组给予蒸馏水饲养。记录小鼠的体质量,分别于第2、4、6和8周处死部分动物后测定肝脏重量并计算肝脏指数。采用试剂盒测定血清中葡萄糖、胰岛素并计算空腹胰岛素抵抗指数(FI-IR),同时测定血清脂质代谢相关生化指标。取小鼠肝脏,行油红O染色和HE染色进行组织病理学观察。结果与正常组相比,30%果糖可使小鼠的体质量、肝重量和肝脏指数显著增加(P0.05)。模型组小鼠的FI-IR持续升高,至第8周时为正常组的4.7倍,差异有统计学意义(P0.05)。高果糖促使小鼠血清中三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白(LDL-C)和游离脂肪酸(FFA)的含量较正常组显著增加(P0.05),血清中高密度脂蛋白(HDL-C)含量显著降低(P0.05)。组织病理学结果发现,模型组小鼠肝脏第2周即出现小脂滴,随着造模时间延长逐步扩大并在第8周肝脏出现明显的弥漫性大脂滴和脂肪变性。结论 30%高果糖饮食可以建立小鼠NAFLD模型,该模型在病理学表现、生化指标等方面与人类的发病特征相似,可用于单纯性果糖诱导NAFLD发病机制和药物治疗的研究。

Establishment and evaluation of a mice model for non-alcoholic fatty liver disease induced using fructose

Objective To investigate the features of the mice model for non-alcoholic fatty liver disease (NAFLD) induced using fructose.Methods C57BL/6 mice in NAFLD group were continuously fed with 30%(w/v)fructose solution for 8 weeks, while mice in normal control group were fed with distilled water.Body weight of mice in both groups was recorded.Liver was weighted and liver index was calculated after mice were sacrificed at week 2, 4, 6 and 8.Serum levels of glucose and insulin were measured and fasting insulin resistance index (FI-IR) was calculated.Indexes of lipid metabolism in serum were detected using corresponding kits.The histopathology of livers was analyzed using oil red staining and hematoxylin and eosin (HE) staining.Results Compared with those in normal control group, the body weight, liver weight and liver index of mice in NAFLD group increased obviously (P<0.05).FI-IR in NAFLD group increased continuously and was up to 4.7 times of that in normal control group at week 8 (P<0.05).Compared with normal control group, NAFLD group showed significantly higher serum levels of triglyceride, total cholesterol, low density lipoprotein and free fatty acid, while markedly lower level of high density lipoprotein (P<0.05).The histopathological results displayed small lipid droplets in liver of NAFLD group at week 2 and obvious diffused macro-vesicular lipid droplets and fat infiltration at week 8.Conclusion Thirty percent fructose diet could successfully establish NAFLD mice model, which shows similar pathological features and biochemical indices with NAFLD patients.This model can be used for the study of pathogenesis and therapy of fructose-induced NAFLD.