高脂喂养联合低剂量链脲佐菌素诱导糖尿病大鼠模型建立及其代谢特征分析

The Establishment of Diabetic Rat Model Induced by Low Dose STZ and High Fat Diet and the Analysis of its Metablic Feature

目的:建立高脂喂养联合低剂量链脲佐菌素(STZ)诱导的2型糖尿病大鼠模型并探讨其代谢特征。方法:35只6～7周龄雄性Wistar大鼠随机分为两组。正常对照组(NC)喂以基础饲料,糖尿病组(DM)喂以高脂高热量饲料,5周后给予DM组一次性腹腔注射STZ(30mg/kg),1周后测血糖,以空腹血糖>11.1mmol/L,并出现多饮、多尿等症状为成模标准。成模大鼠共15只,继续喂以高脂饮食。17周末处死所有大鼠,收集标本,记录体重、肝重,测定空腹血糖(FBG)、甘油三酯(TG)、总胆固醇(TC)、糖化血红蛋白(HbA1c)、糖化血清蛋白(GSP)等生化指标,放免法测定血清肿瘤坏死因子-α(TNF-α),胰岛素浓度(FIN),计算胰岛素敏感指数(ISI)及Homa胰岛素抵抗指数(Homa-IR)。结果:采用高脂喂养联合低剂量STZ一次性腹腔注射可以制作糖尿病大鼠模型,成功率75%,死亡率25%,该模型FBG、HbA1c、TG、TC均显著高于正常对照组,而胰岛素敏感性显著低于正常对照组。结论:高脂喂养联合低剂量链脲佐菌素注射的糖尿病大鼠模型可以模拟2型糖尿病发生的病理生理过程,具有高血糖、胰岛素敏感性下降及血脂异常等代谢特征。

Objective： To develop rat model of diabetes mellitus by high fat diet and low dose streptozotocin （STZ） injection and to explore the metabic feature of the model. Methods： Thirty-five male wistar rats aged of 6 -7 weeks were divided randomly into normal control group and diabetic group, the NC group was fed with regular chow,DM group was fed with high fat diet. After 5 weeks, the rats of DM group were injected by a low dose of STZ （30 mg/kg） once. After one week, the fasting blood glucose （FBG） was detected. The rat whose FBG higher than 11.1 mmol/1 and having the symptoms of polydipsia,polyuria were chosen as the diabetic model （ n = 15）. Alter 11 weeks,all the rats were sacrificed, the blood sample was collected, the body weight, fasting blood glucose （FBG）, fasting serum insulin （FIN）, triglyceride （TG）, total cholesterol （TC）, Glucosylated serum protein （GSP）, and TNF-α were detected. The ISI and Homa-IR were caculated. Result：Iin this study, we made the diabetic model using high fat diet and low dose streptozotocin （STZ） injection, the achievement ratio was 75 % ,and the death rate was 25%. After one week of injection with STZ, the FBG of DM group had gotten was higher than NC group significantly. At the end of the experiment, compared with NC group,DM group got higher FBG, HbAlc, TG, TC, GSP and lower insulin sensitivity. Conclution： The rat model we made in this study have hyperglycemia,hyperlipmia and lower insulin sensitivity, so it can imitate the pathophysiolgy of type 2 diabetes.