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  

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

作　　者：梁海霞[1] 原海燕[2] 李焕德[1] 张松[3] 向大雄[1] 

机构地区：[1]中南大学药学院,湖南长沙410013 [2]中南大学湘雅二医院临床药学研究室 [3]湘雅二医院内分泌科,湖南长沙410011

出　　处：《中国药理学通报》2008年第4期551-555,共5页Chinese Pharmacological Bulletin

摘　　要：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。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 fatenriched 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.

关 键 词：2型糖尿病 胰岛素抵抗 动物模型 链脲佐菌素 

分 类 号：R-332[医药卫生] R363-332