实验性猕猴2型糖尿病模型的建立及评价

Establishment and evaluation of a rhesus monkey model of experimental type 2 diabetes mellitus

背景:目前国内外关于2型糖尿病的非人灵长类动物模型研究报道很少,缺乏标准化制作方法和评价标准。目的:建立一种安全、有效的猕猴2型糖尿病模型及评价方法。方法:将12只猕猴随机分为实验组(n=9)与对照组(n=3),实验组高糖高脂饮食喂养4周后,一次性腹腔注射30 mg/kg链脲佐菌素,建立2型糖尿病模型;对照组注射等量生理盐水。注射第12周,采集外周血血清,测定空腹血糖、血脂、胰岛素、C-肽水平,通过静脉葡萄糖耐量试验、C-肽释放试验检测胰腺胰岛功能,取胰腺、肾脏、肝脏组织行病理组织学检查。结果与结论:(1)注射第12周时,实验组空腹血糖、三酰甘油、总胆固醇均显著高于对照组(P<0.05),C-肽及胰岛素显著低于对照组(P<0.05);(2)实验组静脉葡萄糖耐量试验曲线下面积较对照组增大(P<0.05),C-肽释放试验曲线下面积明显减小(P<0.05);(3)实验组胰腺、肝脏、肾脏组织切片显示均发生了典型糖尿病病理改变;(4)因此认为高糖高脂饮食联合小剂量链脲佐菌素诱导猕猴2型糖尿病模型成功,是一种简单安全、有效的方法。

BACKGROUND： At present, there are few reports about the non-human primate models of type 2 diabetes mellitus in domestic and abroad, so it lacks of standardized production methods and evaluation criteria. OBJECTIVE： To establish a safe and effective type 2 diabetes mellitus model of rhesus monkey and evaluation method. METHODS： Twelve rhesus monkeys were randomly assigned to experimental group（n=9） and control group（n=3）. Rhesus monkeys in the experimental group were fed with high-glucose and high-fat diet for 4 weeks, and intraperitoneally injected with 30 mg/kg streptozotocin to establish models of type 2 diabetes mellitus. Rhesus monkeys in the control group were fed with an equal volume of physiological saline. At 12 weeks after injection, peripheral blood serum was collected to measure fasting blood glucose, lipids, insulin, and C-peptide levels. Intravenous glucose tolerance test and C-peptide release test were used to detect pancreatic gland and pancreatic islet function. Histopathological examination was performed in pancreas, kidney and liver. RESULTS AND CONCLUSION：（1） 12 weeks after injection, fasting blood glucose, triglycerides, and total cholesterol levels were significantly higher in the experimental group than in the control group（P〈0.05）. Insulin and C-peptide levels were significantly lower in the experimental group than in the control group（P〈0.05）.（2） The area under the curve for intravenous glucose tolerance test was increased in the experimental group than in the control group（P〈0.05）. The area under the curve for C-peptide response test was significantly reduced in the experimental group than in the control group（P〈0.05）.（3） The pathological sections of pancreas, kidney and liver showed typical pathological changes of diabetes in the experimental group.（4） It is confirmed that we got high achievement about rhesus monkey models of type 2 diabetes mellitus made by high-glucose and high-fat diet combined with low-dose streptozotocin. It is a feasible, safe and effective method.