目的 高脂饮食(high fat diet, HFD)和西方饮食(western diet, WD)是两种常见的导致非酒精性脂肪肝病(non-alcoholic fatty liver disease, NAFLD)的饮食方式.文章比较了C57BL/6 J小鼠经高脂饮食或西方饮食喂养12周形成NAFLD模型时,肝脏组织中脂质蓄积、肝细胞损伤以及炎性反应等特征,旨在为NAFLD研究中选择合适小鼠模型提供依据.方法 高脂饮食、西方饮食及对照小鼠喂养至12周.禁食8 h后,检测体重和肝重;ISP半自动生化分析仪测定小鼠血清学指标;小鼠肝组织H&E染色检测病理情况;油红O染色分析脂质蓄积;TUNEL染色检测凋亡;Western印迹比较肝脏中脂质代谢及脂性凋亡相关蛋白的表达;Real-time PCR分析肝脏中炎性因子mRNA水平.结果 ① 与对照组比较,高脂饮食和西方饮食组小鼠体重和肝重增加,血糖和血脂水平升高;② H&E及油红O染色结果显示,高脂饮食和西方饮食组小鼠肝脏中出现明显脂质蓄积;③Real-time PCR结果表明,高脂饮食和西方饮食组均引起肝脏内炎性反应;④ TUNEL染色结果提示,西方饮食诱导小鼠肝脏中出现明显肝细胞凋亡及坏死损伤;⑤ Western印迹结果显示,高脂饮食组小鼠肝脏中脂质合成蛋白表达升高,而西方饮食组小鼠肝脏脂性凋亡蛋白表达升高.结论 高脂饮食和西方饮食均导致小鼠出现肥胖、糖脂代谢紊乱及非酒精性脂肪肝病,但高脂饮食组小鼠具有单纯性脂肪肝阶段的典型特征,而西方饮食组小鼠则表现出非酒精性脂肪肝炎的典型特征.%Objective High fat diet(HFD)and Western diet(WD)are two common diets that can induce the mouse models of non-alcoholic fatty liver disease(NAFLD).This study exam-ined the lipid accumulation, hepatocyte damage and inflammation in the livers of C57BL/6J mice fed with HFD or WD for 12 weeks in order to provide evidence for the selection of the optimal mouse model of NAFLD.Methods To establish the NAFLD mouse models, C57BL/6J mice were fed with HFD,WD and chow diet for 12 weeks.After fasting for 8 h,the body weight and liver weight of the mice were measured.Serological indicators were detected by ISP semi-automatic biochemical an-alyzer.The lipid accumulation was determined by H&E and oil red staining, and lipoapoptosis by TUNEL staining.The levels of proteins that were related to lipid metabolism and lipoapoptosis were analyzed by Western blotting.The Mrna levels of inflammatory factors were measured by real-time PCR.Results The body weight, liver weight and blood glucose and lipids were significantly in-creased in HFD mice and WD mice as compared with control mice.H&E and Oil Red staining re-vealed a significant increase in hepatic lipid accumulation in both NAFLD models.The Mrna levels of inflammatory factors were profoundly elevated in both mouse models.TUNEL staining showed ob-vious apoptosis and necrosis of hepatocytes in WD-induced mice.Western blotting showed the ex-pression levels of lipid synthesis-related proteins were greatly increased in the livers of HFD-induced mice,while the levels of lipoapoptosis-related proteins were markedly elevated in the livers of WD-induced mice.Conclusion HFD-induced and WD-induced mice both displayed the common physi-ological characteristics of obesity,disorders of glucose and lipid metabolism and NAFLD.However, HFD-induced mice are characterized by benign steatosis liver and WD-induced mice by non-alcohol-ic steatohepatitis liver.
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