谷氨酸钠联合链脲佐菌素诱导2型糖尿病小鼠模型的建立及评价

Establishment and evaluation of mouse models with type 2 diabetes induced by sodium glutamate combined with streptozotocin

【目的】谷氨酸钠(sodium glutamate,MSG)诱导的肥胖小鼠通过注射链脲佐菌素(streptozotocin,STZ),来轻度摧毁胰岛β细胞,观察是否能诱导出典型的2型糖尿病模型,并对此模型进行评价。【方法】16周龄的雄性MSG肥胖小鼠接受腹腔注射STZ(100 mg/kg)后2周,对其非禁食血糖水平、体质量变化、摄食量、摄水量、口服葡萄糖耐量进行研究,并观察模型动物对二甲双胍的反应性。【结果】MSG联合STZ组小鼠非禁食血糖较MSG肥胖小鼠明显升高(P<0.01),造模期间的体质量增加也明显降低(P<0.01),并有多饮多食的表现,且出现了明显的糖耐量减退(P<0.01),给予二甲双胍后的60及120 min,血糖下降明显(P<0.05,P<0.01)。【结论】MSG联合STZ诱导的小鼠模型具有β细胞功能缺陷和胰岛素抵抗的特征,且糖尿病的典型症状明显,表明腹腔注射STZ能加速MSG肥胖小鼠胰岛β细胞的损伤,能建立典型的2型糖尿病小鼠模型。

【Objective】To study whether streptozotocin(STZ)can induce a typical model with type 2 diabetes(T2 D)in sodium glutamate(MSG)-induced obese mice,and evaluate this kind of model.【Methods】Male MSG-induced obese mice aged 16 weeks were injected with STZ(100 mg/kg)intraperitoneally.After 2 weeks,the non-fasting blood glucose levels,body weight changes,food intake,water intake,oral glucose tolerance were detected,and the response of the model to metformin was observed.【Results】Compared with MSG-induced obese mice,non-fasting blood glucose in the MSG/STZ group was significantly higher(P<0.01),body weight gain was significantly lower(P<0.01)during the modeling period,and MSG/STZ mice had the characters of hyperphagia and hyperposia.Oral glucose tolerance test showed impaired glucose tolerance in MSG/STZ mice(P<0.01).The anti-diabetic drug metformin ameliorated hyperglycaemia in the MSG/STZ mice after 60 and 120 min of administration(P<0.05,P<0.01).【Conclusion】Intraperitoneal injection of STZ can accelerate the damage of isletβcells in MSG-induced obese mice and can be used as a typical model of human T2D that shows significant obesity-induced glucose intolerance and insulin resistance.