Establishment of type 2 diabetes mellitus with early renal injury on spontaneously hypertensive rats
10.3760/cma.j.issn.1001-7097.2010.01.013
- VernacularTitle:应用自发性高血压大鼠建立2型糖尿病早期肾损害模型
- Author:
Houyong DAI
;
Rining TANG
;
Kunling MA
;
Min ZHENG
;
Jie NI
;
Qing LI
;
Xiaoliang ZHANG
;
Bicheng LIU
- Publication Type:Journal Article
- Keywords:
Diabetes mellitus,type 2;
Rats,inbred SHR;
Models,animal;
Insulin resistance;
Diabetic nephropathy
- From:
Chinese Journal of Nephrology
2010;26(1):48-52
- CountryChina
- Language:Chinese
-
Abstract:
Objective To develop a model of type 2 diabetes with early renal injury on spontaneously hypertensive rats (SHR). Methods The 6-week old SHR were fed with the diets enriched with sucrose (20%, W/W), lard (10%, W/W), cholesterol (2.5%, W/W) and chleolate (1%, W/W) to induce insulin resistance. Hyperglycemia was developed by intraperitoneal injection of streptozotocin (STZ, 35 mg/kg). Wistar-Kyoto rats (WKY) were used as normal controls. Rats with plasma glucose (PGL) ≥ 16.7 mmol/L were diagnosed as diabetes. Eight weeks after the induction of diabetes, plasma triglyceride (TG), cholesterol (CHO), glucose, systolic pressure(SP), 24-h urine protein excretion (Upro) were examined in all the rats, and the homeostasis model assessment of insulin resistance (HOMA-IR) was analyzed. Renal pathological changes were studied by immunohistochemical staining and electron microscope. Results After 2 weeks on the high sucrose and fat diets, the model rats exhibited significant increase in basal PGL, TG and CHO levels as compared to control rats (P<0.05, respectively). The insulin resistance was developed in model rats demonstrated by the higher HOMA-IR (5.03±0.38 vs 2.61±0.34, P<0.05). At the end of the experiment, model rats were associated with hypertension. Upro level was significantly increased in model rats compared with that in controls [(57.58±16.54) mg/24 h vs (5.35±1.90) mg/24 h, P<0.01]. The kidney hypertrophy index (KWI) was significantly increased in the model rats compared to controls (P <0.05). Moreover, the diabetic model rats showed glomerular hypertrophy, foot process effacement, micro villous transformation, glomerular basement membrane (GBM) thickening. Conclusion A rat model is successfully established, which presents typical features of human type 2 diabetes and can be served as an ideal model to study the diabetic nephropathy.
