目的 通过高脂饮食建立NAFLD大鼠模型,连续监测4～16周模型动物肝功能、脂质代谢、胰岛素抵抗及肝细胞凋亡在NAFLD进展过程中的变化情况及相瓦关系,为该模型在脂肪肝发病机制、脂肪肝治疗药物评价等方面的应用提供参考依据.方法 SD大鼠50只,除正常对照组外,其余动物饲喂高脂饲料,分别检测4,8,12,16周大鼠血清GLU、CHO、TG、HDL、LDL、GPT、GOT及胰岛素水平,肝脏组织切片进行病理学及细胞凋亡观察,进一步分析大鼠肝功能、脂质代谢、胰岛素抵抗及肝细胞凋亡对肝组织病理改变的影响.结果 模型组大鼠4周后就出现肝功能损伤,脂质代谢紊乱、胰岛素抵抗,肝细胞凋亡8W后明显增加,肝细胞脂变及炎症为肝组织病理变化的主要特征,且造模时间越长,病变程度越严重.结论 经过高脂饲料的喂养,SD大鼠在4～16周内可形成病变程度逐步加重的NAFLD模型,肝功能损伤,脂质代谢紊乱及肝细胞凋亡是引起非酒精性脂肪肝中脂肪变性和炎症的重要因素,该模型可应用于脂肪肝治疗药物评价等方面.%Objective To investigate the pathogenesis of nonalcoholic fatty liver disease ( NAFLD) , provide a reference for the evaluation of fatty liver therapeutic effect, the liver function, lipid metabolism, insulin resistance and liver apoptosis of NAFLO rats established by high cholesterol feeding were continuously monitored from 4 - 16 weeks. Methods 40 NAFLD rats established by high cholesterol feeding were randomly divided into the 4,8,12,16 weeks model group and a group of normal rats were set up for control, the serum GLU、CH0 、TG、HDL、LDL、GPT、GOT and insulin were tested, the liver apoptosis and pathological changes were observed, then analyzed the effect of the liver function, lipid metabolism, insulin resistance and apoptosis on the pathological changes in non-alcoholic fatty liver rats. Results After 4 weeks of highcholesterol feeding, the rats had got the liver injury, disorder of lipid metabolism, insulin resistance. Liver cell apoptosis were increased obviously, and pathological changes were characterized by cell steatosis and inflammatory, the lesions became more serious with time went on. Conclusions Rats established by high cholesterol feeding could get the nonalcoholic fatty liver disease and the lesions became more serious with time over during 4-16 weeks. Lipid metabolism disorder and insulin resistance were the important cause of liver cell steatosis and inflammatory. The model we established is suitable for the evaluation of fatty liver therapeutic effect.
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