小鼠代谢综合征模型的特征及西布曲明的治疗作用研究

目的研究高脂饲料诱导C57BL/6 J小鼠形成代谢综合征(MS)模型的特点,以及盐酸西布曲明对MS小鼠的治疗作用。方法用含10%猪油、2%胆固醇及0.4%胆酸钠的高脂饲料喂养9 wk♂C57BL/6 J小鼠18.5 wk,然后用西布曲明8 mg.kg-1灌胃10 d。实验终点时测定体重、腹腔内脏脂肪及肝脏湿重和肝游离脂肪酸(FFA)含量;取血分离血清测定血脂、血糖和血清胰岛素水平,并计算胰岛素抵抗指数;肝组织进行HE染色和油红O染色,光镜下观察脂肪病变程度。结果模型组小鼠脂肪重量及系数、肝脏重量均明显升高,肝组织切片光镜下可见明显的脂肪病变;血总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)及低密度脂蛋白胆固醇(LDL-C)水平均升高,且以LDL-C升高最为明显;高胆固醇喂养使模型小鼠血甘油三酯(TG)水平降低。西布曲明可改善MS小鼠的中心性肥胖、高血糖、高胰岛素血症和胰岛素抵抗,并进一步降低MS小鼠的血TG水平;但是,西布曲明可增加肝FFA含量,对MS小鼠的肝脏湿重及肝脂肪病变无改善作用。结论高脂饲料长期喂养C57小鼠可成功建立类似人类MS表现的动物模型;西布曲明可改善MS小鼠的中心性肥胖、糖脂代谢异常、增加机体对胰岛素的敏感性,对MS有一定的治疗作用。

Study on the characteristics of metabolic syndrome model in mice and therapeutic effect of sibutramine

Aim To study the characteristics of mouse metabolic syndrome(MS) model induced by high-fat diet and the effect of sibutramine on MS mice.Methods 9-week-old male C57BL/6J mice,fed with high-fat diet(10% lard,2% cholesterol,and 0.4% sodium cholate in basic diet) for 18.5 weeks were treated with saline or sibutramine 8 mg·kg-1 for 10 days.The body weight,wet weight of visceral fat and liver,liver free fatty acid(FFA) content,serum level of lipid,glucose and insulin were examined at the end of the treatment.Results The excessive fat in abdominal cavity was accumulated in MS mice accompanied with hypercholesterolemia,hyperglycemia,hyperinsulinemia,and insulin resistance.In addition,liver weight and grade of hepatic steatosis increased significantly in MS mice.These symptoms in MS mice were similar to those in human beings.After 10 days treatment,sibutramine reduced the obesity related indices,ameliorated glucose and lipid metabolism abnormality,and enhanced insulin sensitivity,but it increased liver FFA content and had no obvious effect on liver weight and hepatic steatosis in MS mice.Conclusions MS model can be induced in C57BL/6J mice by long-term feeding with high-fat diet and sibutramine has a certain therapeutic effect on MS in mice.