高脂饮食诱导肥胖与肥胖抵抗型非酒精性脂肪肝大鼠模型的建立

Induction Method of Non-Alcoholic Fatty Liver Model in Obesity and Obesity-Resistant Rats

目的:利用高脂饲料复制肥胖与肥胖抵抗型非酒精性脂肪肝SD大鼠模型。方法:体质量100±10g的雄性SD大鼠140只,按照体重随机抽取120只用于模型建立,喂食高脂、高能饲料。连续8周后,将体质量大于正常对照组平均体质量+1.96倍标准差的模型大鼠作为肥胖型非酒精性脂肪肝组(NO组),体质量小于正常对照组平均体质量+1.0倍标准差的作为肥胖抵抗型非酒精性脂肪肝组(NOR组)。8周内动态观察大鼠的一般情况、体质量变化,8周末每组随机取8只处死,比较血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、胆固醇(TC)、甘油三脂(TG)水平变化及肝指数、脂体比,观察肝脏形态学改变。剩余20只作为正常对照组,喂食普通饲料。结果:NO与NOR组大鼠体重增长差距逐渐增大,至8w末,NO组体重显著高于NOR组及正常对照组(P<0.01),脂肪重量和脂体比均显著升高,NO组脂肪重量显著高于NOR组(P<0.05,0.01),但脂体比间未见显著差异;NO与NOR组TG、ALT显著升高(P<0.05),其中NO组大鼠血清TG、TC显著高于NOR组(P<0.05);两组肝重量和肝指数均显著升高,NO组肝重量显著高于NOR组(P<0.05,0.01),但肝指数间未见显著差异,两组肝细胞内均弥散大量脂肪空泡。结论:利用高脂饲料成功建立肥胖与肥胖抵抗型非酒精性脂肪肝SD大鼠模型,与人类发病特征相似,为肥胖与非酒精性脂肪的研究提供更有针对性的动物模型。

Objective： To establish obesity and obesity-resistant rats model of non-alcoholic .fatty liver. Methods： 140 male Sprag ue Dawley rats were randomly divide into group control （20） and model （120）, maintained a standard diet and high-energy-fat diet for 8 weeks, respectively. Then the rats of high-energy-fat group were divided into 2 groups s： NO and NOR groups. The rats of body mass higher than nomal ＋1.96 times standard deviation were divided into NO group and the rats of body mass higher than nomal ＋1.0 times standard deviation were divided into NOR group. The general conditions and weight changes were dynamically observed for 8 weeks, and then killed 8 rats of different group. The pathological changes of liver tissues were observed by HE staining. The following indexes were compared among the three groups, including serum levels of triglyceride （TG）, total cholesterol （TC）, alanine aminotransferase （ALT）, aspartate aminotransferase （AST） and liver index, body fat ratio. Results： Starting from the fifth week,the weights of rats were significantly decreased in group control and NOR as compared with those in group NO （P 〈0.01）. The serum levels of ALT, TG, liver weight and index, body fat ratio in group NO and NOR were markedly higher than control （P 〈0.05）. The TC, TG levels and weight of liver in group NO were increased significantly compared with group NOR （P 〈0.05）. And there was no significantly difference between group NO and NOR in liver index and body fat ratio. Light microscopy showed a great number of fat vacuoles in liver cell of group NO and NOR. Conclusion： The obesity and obesity-resistant rat model of non-alcoholic fatty liver can be successfully established within 8 weeks and basically simulating the occurrence and progression of non-alcoholic fatty liver in human beings.