实验性胰岛素抵抗糖尿病大鼠生物学特征

Biochemical and metabolic characteristics of the experimental rats with insulin resistance and diabetes

目的采用高脂饮食联合小剂量链脲佐菌素(STZ)诱导胰岛素抵抗糖尿病大鼠模型,并对其生物学特征进行研究。方法选择健康雄性Sprague Dawley(SD)大鼠20只,按随机数字表分为对照组(普通饲料)和模型组(高脂饲料),每组各10只,自由进食,4周后模型组大鼠予腹腔注射STZ35mg/kg,血糖≥16.67mmol/L者造模成功。造模成功大鼠继续进食高脂饲料。于成模后1、4及8周时观察各组大鼠的体重、血糖、三酰甘油(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)和尿微量白蛋白(MAU)的水平,于成模后1、8周时行腹腔注射葡萄糖耐量实验(IPGTT)及胰岛素耐量实验(ITT)。结果与对照组比较,模型组大鼠注射STZ1周后体重显著增加(P<0.01),注射STZ4、8周后体重显著下降(P值均<0.01);模型组大鼠注射STZ1、4、8周后,TG、TC、LDL-C、血糖及MAU水平均显著升高(P值均<0.01)。IPGTT结果显示,注射STZ1、8周后,模型组AUC均显著高于对照组(P值均<0.01);ITT结果显示,注射STZ1、8周后,模型组注射30、60、120min时血糖下降相对值均显著高于对照组(P值分别<0.01、0.05)。结论高脂饮食联合小剂量STZ诱导的糖尿病大鼠存在糖脂代谢紊乱及胰岛素抵抗。这种造模方法所诱导的伴胰岛素抵抗的大鼠糖尿病更近似于临床上的2型糖尿病的表型特征及发病过程,可用于2型糖尿病及相关慢性并发症的实验研究。

Objective To study biochemical and metabolic characteristics of the rats with insulin resistance and diabetes induced by high fat diet and low dose streptozotocin. Methods Twenty mate SpragueDawley rats were divided into experimental group （high fat diet, n = 10） and control group （normal diet, n = 10） according to random digit table. After 4 weeks, streptozotocin （35 mq/kq） was intraDeritoneallv iniected into therats in experimental group. Rats with plasma glucose≥ 16.67 mmol/L were taken as successful diabetic model and continuously fed with high fat diet. The changes of body weight, plasma glucose, triacylglyceride （TG）, total cholesterol （TO）, high density lipoprotein cholesterol （HDL-C）, low density lipoprotein cholesterol （LDL-C） and microalbuminuria （MAU） were measured at 1, 4 and 8 weeks after modeling. Intraperitoneal glucose tolerance test （IPGTT） and intraperitoneat insulin tolerance test （ITT） were also performed 1 and 8 weeks after modeling. Results Compared with control group, the body weight of the rats in experimental group was significantlyincreased 1 week after injection of streptozotocin （P〈0. 01 ）, but significantly decreased 4 and 8 weeks after injection of streptozotocin （both P〈0. 01）. TG, TO, LDL-C, plasma glucose and MAU in the experimental group were significantly increased 1, 4 and 8 weeks after injection of streptozotocin （all P〈0. 01 ）. IPGTT and ITT showed abnormal glucose tolerance and decreasing insulin sensitivity. Conclusion There are abnormal glycolipid metabolism and increasing insulin resistance in the diabetic rats induced by high fat diet and low dose streptozotocin, which is similar to the pathophysiolgical changes of type 2 diabetic patients in clinic and can be used in the experimental researches of type 2 diabetes and its chronic complications. （Shanghai Med J, 2012, 35：37-40）