中文摘要：

目的：探索一种与人类2型糖尿病肾病（DN）中晚期病变类似的大鼠模型。方法：Wistar大鼠18只,随机分为假手术组和模型组。模型组大鼠行右侧肾切除术并以高脂饲料喂养12周后,进行腹腔葡萄糖耐量实验（IPGTT）及胰岛素耐量实验（ITT）,再以30 mg/kg的剂量腹腔注射链脲佐菌素（STZ）,持续观察24周。每4周检测体重,血糖和24 h尿蛋白水平。实验结束时取血检测血清总蛋白、白蛋白、总胆固醇、三酰甘油、尿素氮和肌酐水平,取肾组织观察病理形态学变化并进行半定量评分。结果：与假手术组相比,模型组大鼠IPGTT及ITT葡萄糖曲线下面积显著增加,动物血糖、胆固醇、三酰甘油、尿素氮及肌酐水平显著升高,白蛋白水平显著降低。模型组肾小球硬化指数与肾小管间质纤维化指数显著高于假手术组,表现出弥漫性肾小球硬化及重度的肾小管间质纤维化。结论：单侧肾切除合并高糖高脂饮食加小剂量STZ腹腔注射可以造成与人类2型DN中晚期病变类似的大鼠模型,其造模方法简单可靠,适合于DN的药效学研究。

英文摘要：

Objective：To develop a rat model similar to the late lesions of human type 2 diabetic nephropathy.Methods：Eighteen male Wistar rats were randomly divided into sham operation group and model group.After right nephrectomy,rats in model group were given sucrose-and fat-enriched diets for 12 weeks,then these rats were intraperitoneally injected low-dose streptozotocin（STZ,30 mg/kg） after IPGTT and ITT and undergone 24 weeks＇ observation.During this period,the body weight,blood glucose and 24 h urinary protein were dynamically examined for each rat every four weeks.Total protein,albumin,cholesterol,triglyceride,urea nitrogen and creatinine in the serum of each rat were measured and renal pathological changes were observed and semi-quantitatively scored at the end of 24th week.Results：Compare with those in the sham operation group,the IPGTT,ITT,blood glucose,TC,TG,urea nitrogen and creatinine of rats in the model group were significantly high,while the total protein and albumin were significantly low.There were diffuse glomerulosclerosis and severe tubulointerstitial fibrosis in the kidneys of model group rats,and these pathological changes were similar to the late Lesions of human type 2 diabetic nephropathy.Conclusion：Unilateral nephrectomy combined high-fat diet and low-dose intraperitoneal injection of STZ can develop a rat model similar to the late Lesions of human type 2 diabetic nephropathy.This method is simple,reliable and suitable for pharmacodynamic study of diabetic nephropathy.