高脂高糖诱导的非酒精性脂肪肝小鼠肝胰岛素底物受体-2的表达

目的探讨非酒精性脂肪肝小鼠肝脏胰岛素受体底物-2(insulin receptor substrate-2,IRS-2)的表达。方法于2002年1月至2003年3月在中国医科大学附属盛京医院内分泌科将30只6~8周龄的雌性SPF级C57BL6J小鼠随机分为3组饲养,其中正常饮食组10只、高脂高糖饮食8周组10只(实验过程中死亡5只)及高脂高糖食16周组10只。测定其血脂、血清胰岛素及空腹血糖、肝功能、肝脏重量、腹部瘦肉及瘦肉含量,肝脏脂质含量及IRS-2蛋白表达。并做肝脏病理检查。结果高脂高糖饮食16周的小鼠腹部脂肪量、血清甘油三酯、空腹血糖、碱性磷酸酶显著高于正常饮食小鼠(P<0.05~0.01);白蛋白及白蛋白球蛋白比值较正常饮食小鼠显著降低(P<0.05)。高脂高糖饮食小鼠肝脏有明显脂肪变性,16周的小鼠较8周的小鼠严重。高脂高糖饮食小鼠的肝脏总胆固醇和甘油三酯含量显著高于正常饮食小鼠,16周时达到正常饮食小鼠的2倍以上;IRS-2表达低于正常饮食小鼠,16周的小鼠高于8周的。结论高脂高糖饮食可使C57BL6J小鼠出现非酒精性脂肪肝,肝脏的IRS-2蛋白表达量低于正常饮食小鼠

Expression of IRS-2 in the Liver of High Fat and Sugar Diet Induced NAFL Mice

Objective To investigate the expression of insulin receptor substrate-2(IRS-2)in the liver of nonalcoholic fatty liver(NAFL)mice.Methods Ten female C57BL6J mice fed with normal diet were served as controls,while fifteen fed with high fat and sugar diet for either 8 weeks(group-A)or 16 weeks(group B)were as NAFL mice models.Abdominal fat mass,total cholesterol(TC),triglycerides(TG),high density lipoprotein cholesterol(HDL-C),fasting blood glucose(FBG)insulin(INS)and liver function,liver weight were measured.And the expression of IRS-2 and the content of lipid in the liver were also detected.Results The abdominal fat mass serum TC,and FBG were significantly higher in high fat and sugar diet fed mice than that in controls(P<0.01,P<0.05),while total protein,albumin and albumin /globulin lower in the mice following 16-week high fat and sugar diet treatment(P<0.05,P<0.05).Serum alkaline phosphatase and aspartate aminotransferase were higher in 16-week high fat and sugar diet treated mice than those in controls(P<0.05).Fatty liver,with the higher content of TG and TC was induced in the mice following the high fat and sugar diet treatment,and reaching 2 times after 16 weeks.The expression of IRS-1 protein was lower in the liver of high fat and sugar diet fed mice than that in normal mice,and it was further decreased in the mice fed for 16 weeks.Conclusion High fat and sugar diet may induce NAFL in C57BL6J mice.The expression of IRS-2 protein in the liver was lower in C57BL6J mice than that in controls.