高脂肪饮食诱导糖尿病小鼠模型

目的]探讨以高脂肪纯化饲料诱导的遗传背景和环境因素共同起作用的C57BL/6J小鼠用于糖尿病药物早期筛选的最短诱导周期.方法]雄性4周龄C57BL/6J小鼠20只适应性喂养7d后随机分为2组,同时饲喂高脂肪饲料.葡萄糖耐受性试验（OGTT）中1组C57BL/6J小鼠口服生理盐水（对照组）,另1组口服磷酸西他列汀（阳性药组）.喂养期间对禁食后血糖（FBG）和体重（BW）进行连续监测,同时进行OGTT试验并监测血浆胰岛素（PINS）水平.结果]高脂喂养1周后小鼠体重升高迅速,并表现为中心型肥胖.第4周FBG和PINS较前3周显著性升高,2周OGTT给糖15 min阳性药组血浆胰岛素水平较对照组有显著性升高.结论]仅饲喂高脂饲料4周的C57BL/6J可用于糖尿病药物药效试验的筛选.该模型方法简单易行,周期短,稳定性好,与人类自然发病过程相似,是较为理想的降血糖药物筛选模型.

Establishment of High Fat Diet Induced Diabetes Mouse Model

Objective] To establish C57BL/6J diabetes mouse model induced with high-fat purified ingredient diets,which may reflect the interaction of genetic background and environmental challenges.Method] After acclimation of the facility for 7days,20 males aged 4 weeks were randomly divided into two groups.One of them （10 mice） will be dosed with saline vehicle in the following OGTT test.And the other groups will be dosed with Sitagliptin as negative control.The body weight （BW）,fasting blood glucose （FBG） and plasma insulin level in the OGTT test will serially measured.Result] The body weight of the 2 groups increased fast and demonstrated central obesity after 1-week high-fat diet.After 4 weeks the FBG and PINS level was significantly higher than previous weeks.The 15 min PINS level of negative control groups.was significantly higher than vehicle group after 2 weeks.Conclusion] Just fed on high fat diet for 4 weeks,C57BL/6J can be used for diabetes early drug screening.With reproducible,simple and period-brief,this model is a very useful animal model in human diabetes drug screening.