非酒精性脂肪肝病小鼠模型的建立及评价

Establishment and evaluation of mouse models of nonalcoholic fatty liver disease

目的运用饲料及药物进行3种不同的建模方式,造非酒精性脂肪肝病(NAFLD)小鼠模型,比较3种模型的特点,为NAFLD药物筛选提供实验基础。方法昆明鼠35只随机分成正常对照组(8只)、高脂饲料组(9只)、高糖高脂饲料组(9只)、高糖高脂饲料加氢化可的松组(9只)。实验4周后,观察各组小鼠体质量、活动情况、肝指数、血清生化指标、肝脏病理学等变化情况。结果相比正常对照组,高脂饲料组体质量增高最显著,高糖高脂饲料组次之,高糖高脂饲料加氢化可的松组体质量低于正常对照组(P<0.05);3种模型肝指数均高于正常组(P<0.05);血糖、血三酰甘油水平增高,肝脏三酰甘油显著高于正常对照组(P<0.05)。3组模型小鼠肝脏病理切片染色均出现肝脏脂肪变性,其中高糖高脂饲料加氢化可的松组肝脏脂肪变性最严重,为最优建模方法。结论不同处理方式都可制备NAFLD模型,但肝脏损伤程度不同。

Objective To establish and compare mouse models in order to evaluate drugs for nonalcoholic fatty liver disease （NAFLD） . Methods Thirty - five Kunming mice were divided intofour groups, namely, normal control group, high - fat diet group, high - fat and fructose diet group, high - fat and fructose plus hydrocortisone group. After four week treatment, the changes in mouse body weight, animal activity, liver index, serum biochemical indexes and liver pathology were detected and analyzed. Results Compared with normal control group, the weight increased most obviously in the high fat group, followed by high fat - fructose group, andthe weight of the high fat- fructose plus hydrocortisonewaslower thanthat of the normal control group （P 〈0. 05） . Andtheliver index in three models was higher thanthat of the normal control group（P 〈 0. 05）. The serum glucose, triglyceride level, hepatic triglyceride were significantly higher than those in the normal control group （ P 〈 0. 05 ） . Among threemodels groups the histopathologic injury in mouse liver tissuesappeared the most serious on he-patic steatosis in the highfat - fructose plus hydrocortisone group,which was optimal method of established model. Conclusion NAFLD mod-el can be prepared by different treatment methods, but the degree of liver damage is different.