高糖高脂饮食诱导的2型糖尿病大鼠模型及其肾病特点

Type 2 diabetes mellitus induced by diets and its features of renal involvement in rat

目的 制备发病过程类似人类 2型糖尿病的动物模型 ,并观察其肾脏病变特点。 方法用高糖高脂饲料喂养 Wistar大鼠诱发胰岛素抵抗 ,然后用亚致病剂量链脲佐菌素 (STZ)腹腔注射 ,诱发高血糖症。 结果 高糖高脂饮食后 1个月 ,大鼠发生高胰岛素血症、胰岛素抵抗和高脂血症。注射 STZ后 ,大鼠血糖升高 ,平均 2 79mg/ dl,血胰岛素降至常规饲料喂养大鼠的水平。其肾脏改变特点 ,临床上表现为持续蛋白尿 ;病理改变为肾小球体积增大、髓袢腔扩张、系膜增生和硬化、基底膜增厚、内皮细胞泡沫样变、出入球动脉透明样变以及间质血管损伤等。 结论 Wistar大鼠用高糖、高脂饮食结合小剂量 STZ注射可成功制备 2型糖尿病模型 ,并具有典型糖尿病肾病病变特点 ,是研究

Objective The study was aimed at developing a rat model that closely simulates the metabolic abnormalities of the human type 2 diabetes mellitus and its renal structural lesions. Methods Female Wistar rats were fed with the diets enriched with sucrose (20%, w/w) and lard (10%, w/w) and cholesterol (2.5%, w/w) and cholic acid (1%, w/w) to induce insulin resistance. Hyperglycemia was developed by intraperitoneal injection in these rats with 25 mg/kg streptozotocin (STZ) after 1 month on the diets. Results Insulin levels increased in response to the diets [(33±2.0 mU/L vs . (18.3±2.04) mU/L in controls, P <0.01)] and insulin resistance was confirmed by insulin suppression test. After STZ injection hyperglycemia [(2.79±1.40) mg/dl vs . (1.04±0.17) mg/dl in controls, P <0.05)] was produced, and plasma insulin decreased to the level of chow fed rats, with hypertriglyceridemia and hypercholesterolemia. The features of renal involvement in the model included overt persistent proteinuria and typical morphological changes. Histologically the earliest abnormality was mainly glomerular hypertrophy. Vascular changes and mild mesangial expansion were come forth at month 3 after diabetes induced. Arteriolar hyalinosis, large vessel atherosclerosis, diffuse glomerulosclersis, thickening of glomerular basement membrane, and vacuolation of endothelinal cell were found after 6 months of diabetes course. Conclusion This novel rat model which is similar to human type 2 diabetes is characterized by moderate hyperglycemia, dyslipidemia, insulin resistance and typical renal lesions. It may provide a particularly advantageous tool for investigations of diabetic vascular complications and pharmacology.