C57BL/6小鼠非酒精性脂肪肝模型的建立研究
Establishment of the nonalcoholic fatty liver disease model in C57BL/6 mice
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摘要: 目的：利用D12492高脂饲料建立小鼠非酒精性脂肪肝（NAFLD）模型，为NAFLD的研究提供参考依据。方法：选用健康雄性C57BL/6小鼠40只，随机分组，正常组20只采用普通饲料喂养，模型组20只采用高脂饲料喂养，建立NAFLD模型。分别在第4周、第8周、第12周、第16周进行体质量、肝质量、肝组织匀浆检测，观察血清丙氨酸氨基转移酶、总胆固醇、低密度脂蛋白及肝脏三酰甘油等指标变化，并进行肝脏病理学检查。结果：模型组小鼠体质量从第4周开始高于正常组小鼠（P<0.05~P<0.01），而肝脏质量从第8周开始高于正常组小鼠（P<0.05）；与正常组小鼠比较，从第8周模型组小鼠丙氨酸氨基转移酶增高（P<0.05~P<0.01）；各时间点模型组血清总胆固醇、低密度脂蛋白均高于正常组（P<0.05~P<0.01）；从第12周模型组小鼠肝组织三酰甘油含量升高（P<0.05和P<0.01）。肝组织HE染色示：从第12周模型组小鼠肝组织见脂肪变，并散布全肝，肝细胞肿胀，细胞质易见脂肪空泡，肝细胞有炎性改变；至第16周模型组小鼠肝脏脂肪变性较前严重，且出现大量炎细胞的浸润。结论：通过高脂饮食诱导的非NAFLD小鼠模型是理想的动物模型，方法简单，重复性强，可为NAFLD的机制研究及药物治疗提供稳定的动物模型。Abstract: Objective: To establish the nonalcoholic fatty liver disease(NAFLD) model in C57BL/6 mice using D12492 high-fat feed,and provide the basis in studying the NAFLD.Methods: Forty healthy male C57BL/6 mice were randomly divided into the control group and model group(20 mice each group).The control group and model group were fed with the normal feed and high-fat feed,respectively.After 4,8,12 and 16 weeks of feed,the body weight,liver weight and liver tissue homogenate were observed,the serum levels of ALT,total cholesterol,low-density lipoprotein and liver triglyceride were detected,and the liver pathology examination was implemented.Results: The body weight after 4 weeks of feed and liver weight after 8 weeks of feed in model group were higher than those in control group,respectively(P<0.05 to P<0.01).Compared with the control group,the serum ALT level in model group after 8 weeks of feed increased(P<0.05 to P<0.01).The levels of serum total cholesterol and low-density lipoprotein in model group at each time-point were higher than those in control group(P<0.05 to P<0.01).Compared with the control group,the content of triglyceride in model group after 12 weeks of feed increased(P<0.05 and P<0.01).The liver tissue staining showed that the liver tissue steatosis,liver cells swelling,fat cavitation in cytoplasm and liver cells inflammatory change were identified in model group after 12-week of feed,and the liver cells inflammatory change aggravated and a large number of inflammatory cells infiltrated in model group after 16-week of feed.Conclusions: The NAFLD model induced by high fat-diet is an ideal animal model,which is easy to establish and repeatable,and can provide stable animal model for the study of mechanism and clinical treatment of NAFLD.
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Key words:
- non-alcoholic fatty liver disease /
- C57BL/6 mouse /
- high-fat diet /
- animal model
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