阿托伐他汀钙致糖代谢异常大鼠模型的建立

Establishment of rats model with abnormal glucose metabolism induced by atorvastatin calcium

目的:建立阿托伐他汀钙致糖代谢异常大鼠模型。方法:将16只健康雄性Wistar大鼠随机分为对照组和阿托伐他汀钙组,阿托伐他汀钙组大鼠给予阿托伐他汀钙50 mg·kg-1·d-1灌胃,对照组大鼠给予等体积去离子水灌胃。两组干预24周后行口服葡萄糖耐量试验和胰岛素释放试验,计算胰岛β细胞功能指数(HOMA-β)、胰岛素抵抗指数(HOMA-IR)及胰岛素敏感指数(HOMA-IS),检测血生化指标并行胰腺组织的病理学检查。结果:与对照组比较,口服葡萄糖耐量试验显示阿托伐他汀钙组30、60、90和120 min的血糖均明显升高(P <0.05);胰岛素释放试验显示阿托伐他汀钙组空腹、30、60、90和120 min胰岛素分泌水平均降低(P <0.05),HOMA-β和HOMA-IR降低,而HOMA-IS升高(均P <0.05);光镜下观察两组胰腺病理组织形态均无明显异常改变。结论:采用大剂量阿托伐他汀钙长时程干预可成功建立他汀致糖代谢异常大鼠模型。

Objective:To explore the method of establishing rats model with abnormal glucose metabolism induced by atorvastatin calcium.Methods:Sixteen healthy male Wistar rats were randomly divided into two groups:the control group(n=8)and the atorvastatin calcium group(n=8).Rats in the atorvastatin calcium group were given atorvastatin calcium(50 mg·kg^-1·d^-1)by intragastric administration and in the control group were given an equal volume deionized water for 24 weeks.Then an oral glucose tolerance test and measures of insulin release were performed.HOMA-β,HOMA-IR and HOMA-IS were calculated.The blood biochemical parameters and pathology of pancreas were also examined.Results:At 30,60,90 and 120 min after glucose intake,the blood glucose levels of the atorvastatin calcium group were all significantly higher than those of the control group(P<0.05).The serum insulin levels before and 30,60,90,120 min after glucose intake in the atorvastatin calcium group were all significantly lower than those in the control group(P<0.05).HOMA-βand HOMA-IR decreased significantly,while the HOMA-IS increased significantly in the atorvastatin calcium group(all P<0.05).No significant differences were found in the pathology of pancreas under an optical microscope between the two groups.Conclusion:Rats model with abnormal glucose metabolism can be successfully established by long term treatment with high dose of atorvastatin calcium.