链脲佐菌素糖尿病肾病大鼠模型的建立及稳定性评价

摘要

Objective To establish a rat model of diabetic nephropathy , with similar laboratory test results and clinical symptoms in patients with diabetic nephropathy and to evaluate the stability of this animal model .Methods Sixty-six healthy male Spraque-Dawley rats were used in this study .Except those in the normal group ,all rat models of diabetic nephropathy were established by unilateral nephrectomy and tail vein injection of streptozotocin (STZ).Dynamic changes of parameters such as body weight , water intake , urine volume , urinary albumin , 24 h urinary protein content , blood glucose level, glycosylated hemoglobin , blood lipid, serum creatinine and urea nitrogen were observed , and renal pathology was also examined to evaluate the success and stability of this rat models .Results The blood sugar , water intake and urine volume were higher than those in the normal group , and body weight loss was observed at 3 days to 16 weeks after STZ administration.The model group rats showed early diabetic nephropathy in 4 weeks, the urinary albumin, 24 h urinary protein and glycosylated hemoglobin were significantly increased than those in the normal group , and the blood lipid , urea nitrogen and creatinine also showed abnormality .The condition was gradually worsening with the extension of time . Conclusion Unilateral nephrectomy and tail vein injection of streptozotocin ( STZ ) induced nephropathy in rats is in accordance with early diabetic nephropathy in humans of both laboratory test results and clinical symptoms .The rat models at 4 to 16 weeks after modeling are in accordance with clinical nephropathy Mogensen stage III .The severity of disease of the rat models is along with the disease course , and is stable and suitable for studies on drug pharmacodynamic evaluation and basic clinical studies on diabetic nephropathy .%目的：建立实验检测和与症状均符合临床糖尿病肾病的大鼠模型并对其稳定性进行评价。方法采用单侧肾切除并链脲佐菌素尾静脉注射建立大鼠糖尿病肾病模型，动态观察16周，以大鼠体重、饮水量、尿量、尿微量白蛋白、24 h 尿蛋白、空腹血糖，糖化血红蛋白、血脂、血清肌酐、尿素氮、肾脏病理等指标评价模型的成功和稳定性。结果糖尿病肾病模型组大鼠造模后3 d ～16周血糖持续升高，饮水量和尿量大幅增多，体质量增长缓慢或负增长，尿微量白蛋白、24 h 尿蛋白定量、糖化血红蛋白升高，血脂代谢异常，尿素氮、肌酐升高。肾脏病理出现糖尿病肾病的典型表现。随时间延长，病情逐渐加重。结论单侧肾切除术后尾静脉注射STZ 复制的糖尿病肾病动物模型与人类糖尿病肾病早期临床症状、病理和化验指标非常相似，在16周内模型稳定，符合糖尿病肾病Mogensen 分期III 期。病情严重程度与病程相一致，适用于药物药效学评价和临床基础研究。