高脂喂养联合链脲佐菌素注射的糖尿病大鼠模型特征

目的观察高脂喂养联合低剂量STZ注射的SpragueDawley(SD)大鼠2型糖尿病模型的代谢特征、病理学以及胰岛分子生物学变化。方法4周龄雄性SD大鼠36只随机分为三组(1)正常对照组(Control)9只,普通饲料喂养。(2)高脂组(HighFatchow,HE)9只,高脂饲料喂养,为普通饲料中添加20%脂肪(猪油和蛋黄粉各50%)和20%蔗糖。(3)糖尿病组(DM)18只。喂养4周后腹腔注射STZ(40mg/kg)。所有大鼠做灌胃葡萄糖耐量(OGTT)试验。放免法测定血清胰岛素,免疫组化染色观察胰岛β细胞的形态学特点,彩色图像分析系统测定胰岛素表达量,RT-PCR测定胰腺β细胞胰岛素mRNA表达水平。结果糖尿病大鼠空腹血糖(FBG)、胰岛素水平(FINS)显著高于Control组和HE组大鼠(P<0.01),空腹血清甘油三酯(TG)和游离脂肪酸(FFA)水平显著高于Control组(P<0.05);胰岛β细胞吸光度(A)显著低于高脂组大鼠(P<0.05),降低11.6%。胰岛素免疫反应阳性区占胰岛百分比显著低于Control组和HE组,分别下降31.9%(P<0.05)和43.1%(P<0.01)。胰岛素mRNA表达水平显著低于HE组(P<0.05)。STZ注射后48h(基线值)大鼠FBG水平的分布情况为A组(FBG<10.0mmol/L)占7/18;B组(FBG10~19.9mmol/L)占5/18;C组(FBG≥20mmol/L)占6/18。STZ注射后9d的OGTT结果与基线值相比,B组OGTT值总体变化最小,A组FBG的变异最大,达到25%。结论高脂喂养联合低剂量STZ注射的糖尿病大鼠模型模拟2型糖尿病发生的主要病理生理过程,具有高血糖、高胰岛素血症以及血脂异常等基本特征。

A Rat Model of Type 2 Diabetes Mellitus Induced by High Fat Chow and Low Dose Streptozotocin Injection

Objective To investigate the levels of blood glucose, triglyceride and total cholesterol, and pathological changes of pancreas,liver and kidney in New Zealand white rabbits fed with high sucrose, high fat and high cholesterol diet. Methods Male New Zealand White rabbits were divided into two groups: control group (n = 10,with normal fodder) and high sucrose, high fat and high cholesterol diet (HD) group (n=10, with 37% sucrose,10% lard,2% cholesterol and 51% normal fodder), and observed for 16 weeks. Once 4 weeks after an overnight fasting, the blood samples of the rabbits were tested for the levels of serum glucose, triglyceride and total cholesterol. At the end of 16 weeks all the rabbits were sacrificed,and a part of pancreas, liver and kidney tissue were sampled for histopathological examination. Results The rabbits in the HD group emerged hyperglycemia, hypercholesterolemia and hypertriglyceridemia subsequently, and no obvious changes were observed in control group. The pancreatic islets from the HD group became atrophied, with loss in number of the islets and cells within them. The nucleus of islet cells were small and deep-dyed. There was an abundance of large vacuolations in cytoplasm. Hepatic steatosis and fibrosis, as well as glomerular hypertrophy and glomerulosclerosis, could be observed in the rabbits of HD group.It is suggested that high sugar, high fat and high cholesterol diet can increase the blood glucose, triglyceride and total cholesterol, and induce pathological changes of pancreas, liver and kidney in New Zealand White rabbits.