Comparison of renal morphology in the Streptozotocin and the SHR/N-cp models of diabetes

• Published in: Laboratory investigation 2004-04, Vol.84 (4), p.452-464
• Main Authors: Gross, M L, Ritz, E, Schoof, A, Adamczak, M, Koch, A, Tulp, O, Parkman, A, El-Shakmak, A, Szabo, A, Amann, K
• Format: Article
• Language: English
• Subjects: Albuminuria - urine; animal model; Animals; Apoptosis; Biological and medical sciences; Biotechnology; Diabetes Mellitus, Experimental - pathology; diabetic nephropathy; Fundamental and applied biological sciences. Psychology; Investigative techniques, diagnostic techniques (general aspects); Kidney - pathology; Kidney Glomerulus - pathology; Kidney Glomerulus - ultrastructure; Laboratory Medicine; Male; Medical sciences; Medicine; Medicine & Public Health; morphology; Pathology; Proliferating Cell Nuclear Antigen - analysis; Rats; Rats, Inbred SHR; Rats, Sprague-Dawley; research-article; Streptozocin; Systole; Transforming Growth Factor beta - analysis
• ISSN: 0023-6837; 1530-0307
• DOI: 10.1038/labinvest.3700052

The Streptozotocin (STZ) model of diabetes is commonly used for studies of diabetic nephropathy although the histological lesions of the kidney are mild and do not resemble those seen in diabetic patients. The SHR/N-cp rat model of type II diabetes spontaneously develops pronounced abnormalities in renal histology. In the present study, we compared renal morphology in the STZ rat and the diabetic SHR/N-cp rat. Sprague–Dawley rats received STZ, developed diabetes after 2 days and were treated with insulin. In the SHR/N-cp rat, obesity is inherited as an autosomal recessive trait. The progeny are either lean (used as controls) or obese and diabetic. After 6 months of observation, STZ and SHR/N-cp rats were killed. The renal damage was evaluated by assessing damage indices and by using stereological techniques. In addition, immunohistochemistry and electron microscopy were performed. The glomerular and tubulointerstitial changes were much more pronounced in the diabetic SHR/N-cp compared to the STZ model. In parallel glomerular PCNA+cells were significantly more frequent and expression of TGF-β and PDGF by immunohistochemistry in glomeruli and in the tubulointerstitial space was more pronounced in SHR/N-cp compared to STZ rats. The glomeruli of SHR/N-cp contained less and larger podocytes as well as smaller mesangial cells embedded in more mesangial matrix compared to STZ. Similarly, less, but larger endothelial cells were found in SHR/N-cp than in STZ rats. The mean glomerular volume was similarly increased in the two models. Albumin excretion was only modestly increased in STZ diabetes, but pronounced in the SHR/N-cp rat. Although the STZ model of diabetes exhibits numerous biochemical sequelae of hyperglycemia, the morphological lesions are unimpressive. In contrast, the diabetic SHR/N-cp exhibits marked structural lesions, particularly podocyte damage and mesangial expansion that promise to make it a more suitable model for investigation of diabetic glomerulosclerosis.