高脂、高胆固醇灌胃诱导2型糖尿病SD大鼠模型的实验研究

目的建立一种简单、经济的2型糖尿病（T2DM）SD大鼠模型.方法 SD雄性大鼠以高脂、高胆固醇灌胃加糖水喂养,诱发胰岛素抵抗,记录饮食、饮水、体重变化,3月后两次腹腔内注射链脲佐菌素（STZ20 mg/kg）诱发高血糖症,继续喂以高脂、高胆固醇、高糖2月,造成实验性2型糖尿病大鼠模型,对其体重、空腹血糖（FGLU）、糖化血清蛋白（FMN）、胰岛素水平（INS）、C肽（C-P）、超敏C反应蛋白（CRP）、甘油三酯（TG）、总胆固醇（TCHOL）进行检测,并计算胰岛素抵抗指数（insulin resistance index,IR-I）.结果 STZ＋HFD组大鼠的FGLU、FMN、INS、C-P、CRP、TG、TCHOL、IRI明显高于HFD组（P〈0.05）,HD组高于ND（P〈0.05）.小剂量链脲佐菌素（STZ,20 mg/kg）分两次给药、毒性小,糖尿病动物模型成模率可达到90%.结论用高脂、高胆固醇灌胃加糖水喂养结合小剂量STZ两次腹腔注射可成功制备T2DM大鼠模型,具有2型DM的葡萄糖和脂质代谢紊乱,同时具有高胰岛素血症和胰岛素抵抗的特征,可作为研究T2DM的理想动物模型.

Induction of Type 2 Diabetes SD Rats Model with Intragastric Administration of High-fat and Cholesterol

Objective To develop a simple and economic method to establish type 2 diabetes Sprague-Dawley rats model.Methods SD rats（200±10） g were admisnistrated intragastrically with high fat,cholesterol and sugar to induce,Insulin Resistance,then the uptake of food,water,and body weight changes were recorded.After 3 months of dietary manipulation,the rats were injected intraperitoneally with low dose of streptozotocin（STZ,20 mg/kg）two times and fed to high-fat diet for another 2 months to establish type 2 diabetes rats model.The body weitht（BW）,the serum levels of FGLU,FMN,INS,C-P,CRP,TG,and TCHOL were detected,and Insulin Resistance Index（IRI）was calculated.Results The HFD＋STZ rats exhibited significant increase in FGLU,FMN,INS,C-P,CRP,TG,TCHOL,and IRI,compared with HFD group（P〈0.05）,the HFD group exhibited significant increase in these indicators,compared with normal group（P〈0.05）.Intraperitoneal injection of low dose of streptozotocin（STZ,20 mg/kg）two times had less toxicity,and the success rate of establishing type 2 diabetes SD rats model reached 90%.Conclusions Intragastric administration of high-fat and cholesterol plus intraperitoneal injection of low dose of streptozotocin two times can establish type 2 diabetes rats model.The model can simulate natural disease progression and metabolic characteristics of type 2 diabetes,and has characteristics of hyperinsulinism and insulin resistance,therefore it can be as an ideal animal model for type 2 diabetes research.