高脂喂养联合低剂量链脲佐菌素诱导的2型糖尿病大鼠模型稳定性观察

目的建立一种简便的2型糖尿病模型并观察该模型的长期稳定性。方法①高脂喂养联合低剂量链脲佐菌素(STZ,45mg·kg-1)诱导2型糖尿病的方法,测定STZ注射后72hSD大鼠的血清空腹血糖(FBG)、甘油三酯(TG)、总胆固醇(CHO)和胰岛素(INS)含量,并用HOMA法计算胰岛素敏感指数(ISI),将72hFBG≥10·0mmol·L-1及ISI≤正常动物均值的大鼠定为糖尿病模型大鼠;同时监测不同时间点大鼠的非空腹血糖(NFBG)、体重、饮食及饮水日摄取量的变化;②连续给予糖尿病模型大鼠灌胃(ig)苯乙双胍(75mg·kg-1)3d,研究该模型的有效性。结果①与正常对照组相比,高脂喂养4wk的大鼠饮食、饮水日摄取量没有明显差异;体重增加,差异无统计学意义。STZ注射后72h时91·7%的大鼠达到成模标准;②该糖尿病动物模型在STZ注射后的12wk内NFBG水平一直较高(>20·0mmol·L-1);③苯乙双胍能降低该2型糖尿病动物模型的NFBG。结论该实验建立的2型糖尿病动物模型造模方法简单、易行,且模型长期稳定。

Observation of stability of a simple type 2 diabetic rat model: combination of high-fat diet-fed and low-dose streptozotocin-induced diabetic rat

Aim To develop a simple rat model of type 2 diabetes that was suitable for long-term pharmacological studies.Methods ① Type 2 diabetes was induced by combination of high-fat diet-fed and low-dose streptozotocin(STZ, 45 mg·kg-1,ip) injection in SD rats, then the concentrations of blood serum fasted blood glucose (FBG), triglycerides (TG), total cholesterol(CHO) and insulin (INS) were determined 72 h after STZ injection, the insulin sensitivity index (ISI) was calculated with HOMA method, rats with a FBG level above 10.0 mmol·L-1 and ISI below the mean level of normal control group's were considered diabetic; meanwhile, non-fasting blood glucose (NFBG) was measured weekly and changes of body weight, food and water intake were also monitored regularly; ② 5 weeks after STZ injection, the response of this model to phenformin (75 mg·kg-1) was tested by oral administration for 3 days to determine the suitability and validity of this rat model for long-term pharmaceutical testing. Results ① Rats fed the fat-enriched diet for 4 weeks weighed 30 g more than the normal chow-fed control ones, but there was no significant difference between the two groups;meanwhile, food and water intake of the two groups was similar.72 h after STZ injection, the success rate of type 2 diabetic animal model reached 91.7%. ② During the experimental period of long-term stability observation, those type 2 diabetic rats always had higher NFBG(>20.0 mmol·L-1). ③ Oral administration of phenformin for 3 days significantly reduced NFBG of those type 2 diabetic rats.Conclusions Establishment of this type 2 diabetic rat model was successful and simple; besides, this diabetic model was stable and suitable for long-term pharmacological studies.