高脂饲喂联合链脲佐菌素诱导的Beagle犬糖尿病模型

目的 应用高脂饲喂联合链脲佐菌素（STZ）构建Beagle犬T2DM模型，并观察其相关特征。方法 将普通级雄性Beagle犬30只随机分为3组：对照组，高脂组，糖尿病模型组，每组10只。糖尿病模型组饲喂高脂饲料同时在饲喂2个月时注射STZ；高脂组饲喂高脂饲料；对照组饲喂普通饲料，连续饲喂5个月。定期测定动物Lee指数、空腹血糖、胰岛素、尿糖，并在3月时进行OGTT试验，试验结束后进行血脂等血液生化检测和肝、胰腺组织病理检查。结果 高脂组和糖尿病模型组高脂饲养2个月后Lee指数显著增加（P<0.01），并出现高胰岛素血症和胰岛素抵抗伴血脂异常；糖尿病模型组STZ注射后空腹血糖显著升高（P<0.01），且持续3个月维持在高血糖水平；而高脂组的空腹血糖无明显变化（P>0.05），糖尿病模型组OGTT试验3 h血糖值>11.1mmol/L，且3 h未恢复，胰腺组织病理学检查出现一定程度的损伤和病变。结论 高脂饲料饲喂诱导Beagle犬胰岛素抵抗和高血脂症，但未能形成高血糖状态，而高脂饲料饲喂联合注射STZ后Beagle犬在出现高血脂症的同时发生胰岛素抵抗，与人类T2DM的胰岛素抵抗伴高血糖、高胰岛素血症和高血脂等典型症状相似。

A beagle model of type 2 diabetes mellitus induced by high fat diet and low dose streptozotocin injection

Objective To investigate the changes of relevant characteristics in the Beagle model of type 2 diabetes mellitus(T2DM) induced by high fat diet and low dose streptozotocin (STZ) injection. Methods Thirty male Beagles were randomly divided into three groups:(1) Control group (n=10), fed with a standard chow. (2) High fat diet group (n=10), fed with high fat diet. (3) Model group (n=10), fed with high fat diet for two months and then given STZ injection. Lee index, fasting blood glucose, serum insulin levels, urine glucose and blood biochemical indexes were regularly detected. Oral glucose tolerance test (OGTT) and histopathological examination were performed. Results After treatment for two months, the insulin resistance and dyslipidemia appeared and Lee index significantly increased in the high fat diet group and model group (P<0.01). In the diabetic beagles, fasting blood glucose levels were prominently increased (P<0.01), as compared with the control group and high fat diet group, and held on a high blood glucose level for three months. Among the three groups, the dogs with OGTT values>11.1 mmol/L and were not restored at three hours, showed some pancreatic histological damages and diseases. Conclusions A beagle model of type 2 diabetes mellitus is constructed, exhibiting some characteristics of human type 2 diabetes mellitus such as hyperglycemia,hyperinsulinism,dyslipidemia and other typical features.