链脲佐菌素制备糖尿病大鼠模型探讨

目的探讨链脲佐菌素(STZ)配合不同饮食建立糖尿病模型的方法,并对模型大鼠学习记忆能力进行考察,为糖尿病的深入研究及药物开发提供可靠的模型。方法雄性SD大鼠70只,随机分为7组,分别为空白对照组(Ⅰ);高糖高脂膳食组(Ⅱ);0周STZ(30 mg/kg)+高糖高脂膳食组(Ⅲ);0周STZ(30 mg/kg)+常规膳食组(Ⅳ);6周STZ(20 mg/kg)+高糖高脂膳食组(Ⅴ);6周STZ(25 mg/kg)+高糖高脂膳食组(Ⅵ);6周STZ(30 mg/kg)+高糖高脂膳食组(Ⅶ)。采用尾静脉注射STZ配合不同饮食制备糖尿病模型,动态监测模型大鼠血糖的变化,生化方法检测大鼠血脂的改变,放免法检测模型大鼠血清胰岛素、胰高血糖素。Morris水迷宫检测不同造模型条件对大鼠空间学习记忆能力的影响。结果与对照组比较,Ⅲ组大鼠于注射72 h后血糖升高明显(P<0.01),至注射第2周血糖升高达顶点(P<0.01),以后逐渐降低,至观察第10周,血糖维持在15 mmol/L(P<0.05)。IV组大鼠于注射72 h后血糖升高,以后迅速降低,至观察第10周,血糖降低至正常水平。Ⅴ、Ⅵ、Ⅶ组大鼠于注射72 h后显著升高,此后呈波浪式变化;随着注射剂量增加,降低程度减慢。高糖高脂饲料喂养10周后,各组大鼠CHO,TG,LDL-C均增加;Ⅲ、Ⅳ、Ⅴ组大鼠血清INS水平较对照组增高,除IV外,各组胰高血糖素均高于对照组。水迷宫试验结果显示,Ⅶ组潜伏期延长,与对照组比较,具有统计学意义。结论 STZ(30 mg/kg)配合高糖高脂膳食能够快速、稳定的建立糖尿病大鼠模型,高糖高脂膳食组6周后尾静脉注射STZ(30 mg/kg)制备模型,血糖升高显著,血清胰岛素水平降低明显,倾向于1型糖尿病模型。

Exploration of the establishment methods of rat models of diabetes mellitus induced by streptozotocin combined with high fat diet

Objective To explore the establishment methods of rat models of diabetes mellitus by streptozotocin combined with different diets and to assess the learning and memory ability of the rat models, and to provide reliable models for diabetes research and related drug development. Methods Seventy male Sprague-Dawley rats were randomly divided into 7 groups, （10 rats each） ： the normal group （I）, high fat diet group.（II）, 0 week STZ （30 mg/kg） ＋ high fat diet group （Ⅲ）, 0 week STZ （30 mg/kg） ＋ standard diet group （IV）, 6 weeks STZ （20 mg/kg） ＋ high fat diet group （V）, 6 weeks STZ （25 mg/kg） ＋ high fat diet group （VI） and 6weeks STZ （30 mg/kg） ＋ high fat diet group （Ⅶ）. Diabetic models were established by intravenous injection of STZ, combined with different diets. The blood glucose （BG） levels were continuously monitored. Biochemical methods were employed to detect the serum lipids. The levels of serum in- sulin and glucagon were also determined. Morris water maze was used to test the changes of learning and memory ability in the model groups. Results Compared with the control, the blood glucose level in the rats of group Ill was significantly in-creased 72 h after STZ injection and reached to a peak 2 weeks after STZ injection （P 〈0.01 ）. Then it decreased gradual- ly, the BG remained at a level of 15 mmol/L 10 weeks after STZ injection （P 〈0.05）. The BG value of the rats in the group IV was increased 72 hours after STZ injection, then it decreased rapidly, and dropped to a normal level 10 weeks af- ter STZ injection. The BG values of rats in the groups V, VI and VII were elevated after the STZ injection and displayed a fluctuating profile in the following period. The range of BG changes depended to the dose of STZ. Compared with the con- trol group, the values of insulin levels of the groups III, IV and V were increased after high fat feeding for 10 weeks. The values of glucagon in all experimental groups were increased except the group VI. The values of CHO, TG, LDL-c were in- creased in all high fat diet-fed rats. Morris water maze test results showed that the escape latency of group VII was signifi- cantly longer than that in the control group. Conclusions Our findings indicate that intravenous injection of STZ （ 30 rag/ kg） with high fat diet is a rapid and stable method for establishing a diabetic model in rats. Indeed, after 6 weeks of high fat diet and subsequent STZ （30 mg/kg） injection, the rats tend to develop type 1 diabetes since they exhibit a high level of blood glucose and low insulin level in the rat models.