Comparison of renal morphology in the Streptozotocin and the SHR/N-cp models of diabetes
Autor: | Marcin Adamczak, Kerstin Amann, A. El-Shakmak, Eberhard Ritz, A. Schoof, Andreas Koch, O Tulp, Marie Luise Gross, András Szabó, A Parkman |
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Rok vydání: | 2004 |
Předmět: |
Male
medicine.medical_specialty endocrine system diseases Systole Urinary system medicine.medical_treatment Kidney Glomerulus Apoptosis Kidney Streptozocin Diabetes Mellitus Experimental Pathology and Forensic Medicine Podocyte Rats Sprague-Dawley Diabetic nephropathy Autosomal recessive trait Transforming Growth Factor beta Proliferating Cell Nuclear Antigen Rats Inbred SHR Internal medicine Diabetes mellitus medicine Albuminuria Animals Molecular Biology business.industry Insulin nutritional and metabolic diseases Cell Biology medicine.disease Streptozotocin Rats medicine.anatomical_structure Endocrinology business medicine.drug |
Zdroj: | Laboratory Investigation. 84:452-464 |
ISSN: | 0023-6837 |
DOI: | 10.1038/labinvest.3700052 |
Popis: | 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-beta 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. |
Databáze: | OpenAIRE |
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