Análise temporal da função renal em camundongos hipercolesterolêmicos

• Autor(a) principal: Balarini, Camille de Moura
• Data de Publicação: 2009
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da Universidade Federal do Espírito Santo (riUfes)
• Texto Completo: http://repositorio.ufes.br/handle/10/7937
• topic: Fisiologia; 61

Aging is a physiological process with deleterious consequences for renal function, which could be exacerbated when concurrent with pathological situations, such as dyslipidemia. The aim of this study was to determine whether hypercholesterolemia and aging could affect the renal function in mice. Male hypercholesterolemic apolipoprotein E-deficient (ApoE, n=18) mice and their age-matched C57BL/6 (C57, n=18) control mice were studied at 2-, 4- and 8-month-old. At each time point, animals were placed in metabolic cages for 24 hours in order to analyze urine volume and urinary creatinine determination. Samples of blood were collected for serum cholesterol, urea and creatinine determination. Glomerular filtration rate (GFR) was estimated by the creatinine clearance. Urine samples were submitted to polyacrilamide gel electrophoresis to verify the presence of albuminuria and renal senescence was evaluated by senescence associated beta-galactosidase activity technique. Glomerular morphometric measurements were evaluated in 10 hematoxilin-eosin stained sections (10 µm-thickness) and mesangial expansion was evaluated by Periodic Acid Schiff staining. Expression of nNOS was measured by Western Blotting. For statistical analysis, 2-way ANOVA was used followed by Fisher’s post hoc. Differences were considered statistically significant when p<0.05. Total plasma cholesterol was increased about 5-fold in ApoE mice at both time points compared with C57 animals (C57 2 months: 94.0±5.1; ApoE 2 months: 606.0±91.3; C57 4 months: 97.1±7.2; ApoE 4 months: 493.7±44.0; C57 8 months: 116.0±10.0 and ApoE 8 months: 636.1±76.4). At 2-month-old, GFR was already markedly reduced in ApoE (187±28) when compared to C57 mice (358±92). Aging caused a significant reduction of GFR in C57 mice (4 months: 211±60 and 8 months: 81±14) although did not worse this parameter in ApoE mice (4 months: 128±42 and 8 months: 93±18). In addition, serum urea was significantly increased in ApoE animals already at 2-month-old compared with C57 mice and this difference is not time-dependent (C57 2 months: 39.8±5.2; ApoE 2 months: 64.5±7.6; C57 4 months: 41.1±7.8; ApoE 4 months: 73.5±17.9; C57 8 months: 49.1±3.5; ApoE 8 months: 77.3±7.5). Only ApoE mice at 8-montold presented albuminuria. Aging promoted markedly renal senescence in C57 animals and this occurred earlier in ApoE. No differences were found in glomeruli number nor glomerular tuft area. A significant mesangial expansion was already observed at 2-month-old ApoE mice (ApoE: 35.3±0.8 vs. C57: 29.8±0.9) and this condition was aggravated by aging in ApoE mice (4 months: 40.4±1.2 and 8 months: 41.5±2.7) and induced in age-matched C57 animals (4 months: 37.8±1.3 and 8 months: 37.4±0.7). No differences were found in nNOS expression due to neither aging nor hypercholesterolemia. These data show that hypercholesterolemia can enhance the age-related loss of renal function.