饮食诱导肥胖与肥胖抵抗型非酒精性脂肪肝大鼠的对比研究

目的 观察饮食诱导肥胖与肥胖抵抗型非酒精性脂肪肝大鼠相关指标的变化。方法 140只雄性SD大鼠,体质量(100±10) g。随机抽取20只作为正常对照组,喂食普通饲料;剩余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(O-N组),体质量小于正常对照组平均体质量+1.0倍标准差的模型大鼠作为肥胖抵抗型非酒精性脂肪肝组(OR-N组),并挑出O-N组体质量增加最多的20只和OR-N组体质量增加最少的20只作为实验对象。8周内动态观察大鼠的一般情况和体质量变化,8周末每组随机取8只处死,比较血清丙氨酸转氨酶(ALT)、总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白(HDL)、瘦素(leptin)含量、胰岛素敏感指数(ISI)及能量利用率变化,并观察肝脏形态学改变。结果 O-N与OR-N组大鼠在喂养期间体质量差距逐渐增大,至8周末,O-N组体质量显著高于OR-N组及正常对照组(P<0.01);两组ALT、TG、leptin均显著升高(P<0.05,P<0.01),O-N组大鼠血清TC、TG、leptin、能量利用率均显著高于OR-N组(P<0.05,P<0.01);O-N组大鼠ISI、HDL显著低于OR-N组和正常对照组(P<0.01,P<0.05);O-N组与OR-N组肝细胞内弥散大量脂肪空泡。结论 高脂、高能饲料在诱导SD大鼠发生非酒精性脂肪肝的同时,发生肥胖与肥胖抵抗,血清leptin和胰岛素水平的变化可能与其直接相关。

A comparative study of diet-induced obesity and diet-induced obesity-resistant non-alcoholic fatty liver in rats

Objective To observe the changes of non-alcoholic fatty liver related indices in diet-induced obesity-resistant rats and diet-induced obesity rats. Methods A total of 140 male Sprague Dawley(SD) rats were randomly divided into normal control group (n=20, normal diet for 8 weeks) and model group (n=120, high fat diet for 8 weeks). The rats of model group were further divided into 2 groups: O-N (obesity with non-alcoholic fatty liver) and OR-N (obesity-resistance with non-alcoholic fatty liver) groups. The rats with body mass higher than mean +1.96 folds standard deviation were included in O-N group and those with body mass lower than mean +1.0 fold standard deviation were included in OR-N group. The animals with the top 20 weight gains in the O-N group and those with the least 20 weight gains in OR-N group were used in the present study. The general conditions and weight changes of rats were dynamically observed for 8 weeks. Eight rats were sacrificed in each group at the end of the 8th week and the following indices were compared among the three groups,including serum levels of alanine aminotransferase (ALT), total cholesterol(TC), triglyceride(TG), high-density lipoprotein (HDL), insulin sensitivity index(ISI), leptin, energy utilization and body fat ratio. The pathological changes of liver tissues were observed by H-E staining. Results The weight difference of rats in the O-N group and the OR-N group gradually increased; at the end of the 8th week, the weight of rats in O-N group was significantly higher than those in the OR-N group and the normal control group(P<0.01). The serum levels of ALT, TG, and leptin were significantly increased in both O-N and OR-N groups (P<0.05,P<0.01). The TC, TG, leptin levels and energy utilization in O-N group were significantly higher than those in OR-N group (P<0.05, P<0.01). The HDL and ISI levels in the O-N group were significantly lower than those in the OR-N and normal control groups (P<0.01, P<0.05). Light microscopy showed a great number of fat vacuoles in the liver cells of O-N and OR-N groups. Conclusion High fat diets can induce SD rat to develop non-alcoholic fatty liver with obesity and obesity-resistance.Increase in serum leptin and ISI may play a role in resisting diet-induced obesity and non-alcoholic fatty liver of rats.