高成模率和高稳定性的糖尿病大鼠模型制备——高脂高糖膳食+STZ体重联合体表面积法构建糖尿病大鼠模型

The study of establishing a highly stable and successful diabetic rat model

目的构建高成模率和高稳定性的高血糖伴胰岛素抵抗(IR)大鼠模型。方法 Wistar大鼠高脂高糖膳食4 w后,腹腔注射2次链脲佐菌素(STZ),进行间隔时间及注射剂量遴选实验。选用上述最佳造模法进行药效学及模型稳定性实验:将成模大鼠随机分为模型对照组和二甲双胍治疗组,4 w后检测药物影响;模型对照组(1/2)再继续普食饲养8 w,判断模型稳定性。结果 2次STZ腹腔注射间隔时间2 d组,成模率最高(90%),注射剂量以25 mg/kg+m2成模率最高(100%)。此法造模,所有大鼠禁食血糖、随机血糖均达糖尿病标准,且二甲双胍治疗有效;模型对照组无1例自愈。结论高脂高糖4 w+2次STZ腹腔注射(25 mg/kg+m2,间隔2 d)可成功制备高成模率和高稳定性的伴IR的糖尿病大鼠模型。

Objective To establish an efficient and stable rat model of hyperglycemia and IR. Methods Wistar rats were fed with high-fat and high-sucrose diet for 4 w followed by 2 times intraperitoneal streptozotocin （STZ） injections. Optimal STZ doses and time intervals were analyzed. Pharmacodynamics and stability test were assessed on the optimized rat model, which were randomly divided into model and mefformin treatment groups, and then detected drug effects after 4 w treatment. Rats in model control group（1/2） were continuously fed with normal diet for 8 w, the model＇ s stability was judged. Results Two intraperitoneal STZ injections （25 mg/kg） at the 2-day interval group was demonstrated the highest success rate of model establishment （ 90% ）. Two 2-day interval STZ injections （25 mg/kg ＋ m^2 ） showed a 100% success rate of model establishment. According to this modeling method, all rats were met diagnostic criteria for diabetes in terms of fasting and random blood glucose levels and demonstrated increased lipid and glycosylated serum protein levels, decreased insulin levels, as well as abnormal glucose and insulin tolerance. Metformin treatment resulted in effective decrease in blood glucose levels. Rats in the model control group were continuously fed with normal diet for 8 w and their fasting and random blood glucose levels still met diagnostic criteria for diabetes. No mortality was observed. Conclusions Four weeks high-fat high-sucrose diet followed by two 2-day interval STZ injections （25 mg/kg ＋ m^2 ） could be successfully used to establish a rat model of hyperglycemia and IR with 95% efficiency of model establishment and stability.