吡格列酮对大鼠非酒精性脂肪性肝炎干预的实验研究

目的　用吡格列酮对试验动物进行干预 ,探讨胰岛素抵抗与非酒精性脂肪性肝炎的关系。方法　雄性SD大鼠 5 0只随机分组。正常对照组喂饲普通饮食 ,高脂模型组喂饲高脂饮食 ,给药组分别在喂饲高脂饮食 4周后、9周后分别给予吡格列酮灌胃 ,并分别在 9周末及 14周末处死各组大鼠 ,测定血清转氨酶、血糖、血脂、胰岛素及FFA水平 ,观察肝组织学改变。结果　 9周后模型组大鼠呈现明显腹型肥胖 ,产生脂质代谢紊乱及胰岛素抵抗 ,肝脏出现肝细胞脂肪变性 ,给药组各项指标均有明显改善 ;14周后模型组大鼠血清转氨酶水平升高 ,肝脏出现炎细胞浸润 ,除肝组织炎症外 ,给药组其他指标均有不同程度的改善。结论　胰岛素抵抗在大鼠肝脏脂肪变的发生中起到关键作用 ,与脂肪肝发生炎症坏死关系甚密切 :吡格列酮可明显改善高脂饮食诱发大鼠肝脏的脂肪变性 ,对炎症变化作用不明显

The effect of pioglitazone on the establishment of rat model of nonalcoholic steatohepatitis

Objective To explore the relationship of insulin resistance and nonalcoholic steatohepatitis, and to evaluate the effects of insulin sensitizer pioglitazone on the model rats.Methods Fifty male SD rats were randomly allocated into 5 groups.Normal rats were fed with general diet. Model rats were fed with high fat diet. Medication rats were given insulin sensitizer pioglitazone orally after fed with high fat food 4 and 9 weeks. After 9 and 14 weeks,the rats were sacrificed. Body weight, body length,liver wight,transaminase level,blood glucose,triglyceride,cholesteral,free fatty acid,insulin level and liver histology were detected.Results After 9 weeks, abdomen_form obesity,lipid metabolism and insulin resistance,and pathology of hepatocyte steatosis in livers were observed in model rats. And every marker of medication rats was improved treated with ingroup pioglita zaone. After 14 weeks, insulin resistance level had no progress, transaminase level increased, hepatocyte steatosis developed and livers presented the pathology of inflammation cell infiltration. And every marker of medication rats except inflammation cell infiltration was improved.Conclusion Insulin resistance play a key role in occurrenc of hepatocyte steatosis,but has no intimate relation with inflammation. Pioglitazone is approved to be operative in prevention and cure hepatocyte steatosis,but had no effect on inflammation.