Alterações renais gênero-dependentes em ratos com insuficiência renal crônica

• Ano de defesa: 2011
• Autor(a) principal: Lemos, Carla Cavalheiro da Silva
• Orientador(a): Bregman, Rachel
• Banca de defesa: Boim, Mirian Aparecida , Lugon, Jocemir Ronaldo , Gomes, Carlos Perez , Mandarim-de-lacerda, Carlos Alberto , Guimarães, Marco Antonio Mello
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade do Estado do Rio de Janeiro
• Programa de Pós-Graduação: Programa de Pós-Graduação em Ciências Médicas
• Departamento: Centro Biomédico::Faculdade de Ciências Médicas
• País: BR
• Palavras-chave em Português: Insuficiência renal crônica; Matriz extracelular; Glomérulo; Gênero; Castração; Proteinuria; Glicosaminoglicanos; Alfa-actina; Rins Doenças; Hormônios sexuais; Glicosaminoglicanas; Glomerulos renais
• Palavras-chave em Inglês: Chronic renal failure; Extracellular matrix; Glomeruli; Gender; Castration; Proteinuria; Glycosaminoglycans; Alfa-smooth-muscle-actin
• Área do conhecimento CNPq: CNPQ::CIENCIAS BIOLOGICAS::FISIOLOGIA::FISIOLOGIA DE ORGAOS E SISTEMAS
• Link de acesso: http://www.bdtd.uerj.br/handle/1/8565

Chronic renal failure (CRF) is characterized by adaptive mechanisms secondary to the loss of functioning nephrons. Glomerular hemodynamics alterations, cellular proliferation, inflammatory cells influx, imbalance between synthesis and degradation of the glomerular extracellular matrix (GECM) and loss of charge and/or size selectivity of the glomerular basal membrane are pointed as mechanisms leading to mesangial expansion and glomerulosclerosis. Additionally, participation of gender related hormones on renal function and progression of CRF have been suggested. We evaluated the effect of castration in renal alterations in males (M) and females (F) Wistar rats, after 30 days of 5/6 reduction of renal mass (CRF). The animals were castrated (c) at 5 weeks old and 7 weeks old 5/6 and sham nephrectomy were done. Groups: Control (C) CM, CM sham, CMc, CF, CF sham, CFc, CRFM, CRFMc, CRFF, CRFFc. CRFM group showed higher proteinuria followed by increased mesangial expansion and α-actin immunostaining. Concomitant higher concentration of heparan sulfate (HS) was also observed when compared to CRFF (p<0.05). These alterations were reduced in CRFMc group. Podocyte morphology analysis through electronic microscopy showed few disorders of foot processes in CRF groups Overall, CRFF group showed fewer alterations compared to males, and a reduction of HS was observed in association with PTN. Castration did not change this profile in female rats. Data suggest that male hormones may participate in the maintenance of the mesangial equilibrium and that PTN collaborated with the mesangial expansion process. Additionally, the higher concentration of HS in CRFM suggest that the remodeling process of the GECM, included a synthesis of de novo HS, that presented a functioning defect, compromising the glomerular filtration barrier and, ultimately corroborated with the loss of its selectivity and consequently with a higher PTN. This set of results leads us to conclude that PTN appears early in the course of CRF, may contribute to renal GECM imbalance and, the mechanisms involved in these processes seem to be influenced by gender-related hormones. In addition, male hormones seem to aggravate renal alterations contributing to a poor prognosis of CRF progression in male rats.