2型糖尿病大鼠模型的建立与评价

Establishment and Evaluation of Rat Models of Type 2 Diabetes Mellitus

目的:建立具有胰岛素抵抗特征、发病过程近似于人类2型糖尿病的动物模型。方法:雄性Wistar大鼠喂以富含不饱和脂肪酸的特殊高脂肪膳食5周,诱发出胰岛素抵抗,继之以小剂量链脲佐菌素(STZ,25mg/kg,腹腔注射)导致胰岛素代偿性分泌障碍,诱发高血糖症。应用正常血糖-高血浆胰岛素钳夹技术评价大鼠的胰岛素敏感性。结果:与常规饲料喂养大鼠相比,高脂膳食组的葡萄糖输注率显著降低,空腹血浆胰岛素显著升高。STZ注射后1周高脂膳食组大鼠血糖中度升高,血胰岛素下降,但仍高于普通饲料喂养组,且高脂血症和胰岛素抵抗继续存在。高脂饲料喂养组及高脂饲料+小剂量STZ注射组大鼠的葡萄糖输注率显著低于正常对照组。结论:通过高脂膳食结合小剂量STZ注射成功复制出了实验性2型糖尿病动物模型,它是研究2型糖尿病发病机制、药物研究和胰岛素抵抗相关疾病的理想动物模型。

Objective： To establish an animal model similar to the metabolic abnormalities of human type 2 diabetes mellitus with insulin resistance.MethodS： Adult male Wistar rats were fed with high-fatty （59% of calories-fat） diet that contained unsaturated fatty acid for 5 weeks to induce insulin resistance, then streptozotion（STZ, 25 mg/kg） was injected intraperitoneally to result in insulin secretion defect and hyperglycemia, euglycemic-hyperinsulincmic clamp technique was performed in rats to estimate their insulin sensitivity.Results： Glucose infusion rates （GIR） in the rats with high-fat diet decreased and fast plasma insulin increased compared with the control group. Based on the high-fat diet, the rats were injected intraperitoneally with lowdose streptozotocin to establish type 2 diabetes mellitus model. One week after STZ injection,blood glucose moderate increased, plasma insulin decreased but still higher than that in regular chow-fed rats, with insulin resistance and dyslipidemia still existed. GIR was obviously lower in rats with the high-fatty diet group and the high fatty plus low dose STZ injection group than that of the control group. Conclusion; Type 2 diabetes mellitus animal model is successfully reproduced by using the high fatty diet plus low dose STZ injection.It may provide a perfect animal model for investigating type 2 diabetic mechanism and pharmacology, also be used to research insulin resistance and related diseases of human beings.