›› 2002, Vol. 22 ›› Issue (2): 78-82.

• 论文 • 上一篇    下一篇

大鼠糖尿病性肾病模型的建立

  

  1. 中国科学院上海药物研究所 200031
  • 收稿日期:2002-01-23 出版日期:2002-01-25 发布日期:2013-03-19

Establishment of Diabetic Nephropathy Model in Rat

  1. Shanghai Institute of Materia Medica,Chinese Academy of Science,Shanghai 200031, China
  • Received:2002-01-23 Online:2002-01-25 Published:2013-03-19

摘要: 给单侧肾切除雄性Wistar大鼠的阴茎背静脉注射35mg/kg链脲霉素引发糖尿病,在5个月的实验过程中,大鼠的血糖水平一直处于稳定的中、高度状态。在实验第1周大鼠体重明显下降,以后体重不再下降,也不增重,而对照组大鼠在5个月的实验过程中体重持续增加。实验开始5个月后,糖尿病大鼠的平均动脉压和肾脏血管阻力均显著高于对照组(P<0.001),肾脏血浆流量则显著低于对照组(P<0.01),导致滤过分数显著上升(P<0.001),糖尿病大鼠的尿量比对照组明显增加,实验4周起24 h的蛋白尿就有显著增加(36.8±3.6 mg vs.21.5±1.7 mg,P<0.01),并且随着时间的延续呈进行性升高。无论是心脏与体重比(0.35%±0.01% vs.0.24%±0.01%, P<0.001),还是左肾与体重比(0.99%±0.07% vs. 0.39%±0.01%, P<0.001),糖尿病大鼠都显著高于对照组。结果提示,给单侧肾切除的大鼠静脉注射低剂量STZ可以诱发糖尿病性肾病模型,具有高血压、进行性蛋白尿、肾功能不良的体征。

关键词: Wistar 大鼠, Ⅰ型糖尿病, 肾病, 高血糖, 蛋白尿

Abstract: Type I diabetes mellitus were made in Wistar rats by intravenous injection of 35 mg/kg streptozotocin freshly dissolved in citrate-buffered saline solution. Stable moderate hyperglycemia was maintained throughout the duration of the experiment,without receiving any insulin injection. Body weights were markedly reduced at 1 week after induction of the diabetes and maintained throughout the experiment in the untreated diabetic rats,whereas non-diabetic control rats gained weight during the 5-month follow-up. Blood pressure (BP) and renal function data at 5 months after induction of diabetes were summarized.The untreated uninephrectomized diabetic rats developed hypertension with mean arterial pressure (MAP) of 128±2 mmHg under anesthesia. Renal vascular resistance (RVR) was markedly elevated·in the untreated diabetic rats as compared to that in controls (P<0.001),leading to a significant lower renal plasma flow (RPF)(P<0.01).Glomerular filtration rate (GFR) was comparable between untreated diabetic rats and controls.Thus,Filtration fraction (FF) rose significantly (P<0.001).Urine flow rate was also markedly increased in the untreated diabetic rats.Un-treated diabetic rats showed a significant increase in urinary protein excretion as early as 4 weeks after induction of the disease (36.8±3.6 vs. 21. 5±1.7,P<0.01 in control rats at week 4) , with a substantial progressive increase of this value over time. A ratio of the heart weight to the body weight was 3. 5±0.1 to 2.4±0.1 (P<0.001) and the left kidney weight to the body weight was 9.9±0.7 to 3. 9±0.1 (P<0.001).Both ra-tios were markedly higher in untreated diabetic rats as compared to those in controls. Thus, the STZ-injected uninephrectomized rats developed overt diabetic nephropathy,as evidenced by the development of hypertension,progressive proteinuria and renal dys-function.

Key words: Wistar rats, Type I diabetes mellitus, Nephropathy, Hyperglycemia, Urinary protein