| Background and objective: Diabetic nephropathy is the principal cause of end-stage renal failure in developing countries, with renal disease as a major cause of morbidity and mortality in the diabetic population. An interaction of metabolic and hemodynamic factors has been considered a traditional aspect involved in the development of renal lesions in patients with type 1 or type 2 diabetes. However, the recent study in vivo and in vitro evidence demonstrated inflammatory phenomena are necessary to translate primary insults into chronic progressive renal disease in diabetic state. Macrophages in diabetic kidneys were found in the glomerular tuft and around dilated tubules, which were sites shown to express macrophage chemokines. Large-scale clinical trails and experimental study have indicated that blocking renin-angiotensin system (RAS) with angiotensin converting enzyme (ACE) inhibitors or angiotensin II receptor blockers has changes profoundly the therapeutic approach to diabetic nephropathy, and may improve the survival and the quality of life of diabetic patients. However, the effect of blocking RAS on renal macrophage infiltration and involved mechanism in experimental diabetes has not been clearly delineated. The present study aimed at the evaluation of the action of enalapril (an AECI) on oxidative stress, macrophage infiltration and expression of MCP-1,ICAM-1 and CTGF in kidney in diabetic rat induced by STZ.Methods: Thirty adult male Sprague-Dawley rats were randomly separated into three groups: control group (n=10), model group (n=10), model group treated with enalapril (enalapril group, n=10) .To induce an experimental model of diabetes, rats received a single intraperitoneal injection of STZ (65mg.kg-1) after uninephrectomy. Enalaprilgroup received enalapril lOmg'kg '?d ' by gavage. 8 weeks after STZ injection, the following determinations were done in samples: 1. plasma glucose (BG) was determined according to standard methods, 24 hours urinary albumin excretion rate (AER) was determined by EIA method; 2. malondiadehyde (MDA), superoxide diamutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) in renal tissue were determined by spectrophotometric method; 3. kidney lesions were evaluated using periodic acid-Schiff staining (PAS) staining; 4. immunohistochemistry for ED-1 (monocytes/ macrophages), MCP-1 , ICAM and CTGF were performed by streptavidin-biotin comblex (SABC) technique.Results: 1. Clinical and metabolic parameters: Rats in model group had reduced body weight gain and increased blood glucose levers. No effects on blood glucose were observed with enalapril treatment, enalapril treatment was significantly associated with body weight gain. As shown previously, kidney enlargement was observed in model group, which was significantly reduced by treatment with enalapril. In group model group, AER was significantly increased when compared to group control. Treatment with enalapril attenuated the increase in AER in the diabetic rats.2. Renal histology: Rats in model group had an increase in the glomerular tuft and mesangial area and glomerular volume when compared with the values in group control, enalapril treatment ameliorated the increase of the glomerular tuft and mesangial area and glomerular volume. Rats in model group had an increase in the tubulointerstitial injury index when compared to group control, enalapril treatment was associated with a reduction in tubulointerstitial injury index as compared with model group, but this did not reach statistical significance. 3. Oxidative stress: MDA content and activities of AOE were examined in kidneys harvested at the end of the experiment. The renal content of MDA was higher in model group than that in group control, enalapril treatment was associated with a significant reduction in the MDA content of the kidney. In model group,... |
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