RESUMO
The caspase-3-cleaved presence was evaluated in this study in the heart of irradiated rats, during the decline of ventricular function. Female Wistar rats were irradiated with a single dose of radiation (15 Gy) delivered directly to the heart and the molecular, histological and physiological evaluations were performed at thirteen months post-irradiation. The expressions of procollagen type I, TGF-ß1 and caspase-3-cleaved were analyzed using Western blotting. Cardiac structural and functional alterations were investigated by echocardiography and electron microscopy. In the irradiated group, the levels of procollagen type I, TGF-ß1 and caspase-3-cleaved are increased. Significant histological changes (degeneration of heart tissue and collagen deposition) and functional (reduced ejection fraction) were observed. Data suggest that the cardiac function decline after exposure to ionizing radiation is related, in part, to increased collagen and increased caspase-3-cleaved.
Assuntos
Caspase 3/metabolismo , Colágeno Tipo I/metabolismo , Coração/efeitos da radiação , Miocárdio/enzimologia , Fator de Crescimento Transformador beta1/metabolismo , Animais , Western Blotting , Relação Dose-Resposta à Radiação , Ecocardiografia , Ativação Enzimática/efeitos da radiação , Feminino , Microscopia Eletrônica de Transmissão , Miocárdio/ultraestrutura , Ratos , Ratos WistarRESUMO
Foi avaliada neste estudo a presença de caspase-3-clivada no coração de ratos irradiados durante o declínio da função ventricular. Ratas Wistar foram irradiadas com uma dose única de radiação (15 Gy) diretamente no coração e as análises molecular, histológica e fisiológica foram realizadas treze meses pós a irradiação dos animais. As expressões de procolágeno tipo I, TGF-ß1 e caspase- 3-clivada foram analisadas usando Western blotting. Alterações cardíacas estruturais e funcionais foram investigadas por meio de ecocardiografia e microscopia eletrônica. No grupo irradiado, os níveis de procolágeno tipo I, TGF-ß1 e caspase-3-clivada estão aumentados Alterações histológicas importantes (degeneração do tecido cardíaco e deposição de colágeno) e funcionais (fração de ejeção reduzida) foram observadas. Dados sugerem que o declínio da função cardíaca após a exposição à radiação ionizante está relacionado, em parte, com aumento do colágeno e da caspase-3-clivada.
RESUMO
CD8+ T lymphocytes are considered an important cell population involved in the control of parasitaemia and mortality after Trypanosoma cruzi infection. However, despite recent developments in this field, the mechanism whereby this control is exerted is still not completely understood. Here we have used perforin knockout (-/-) mice infected with Y strain T. cruzi in order to evaluate specifically the participation of the perforin-based cytotoxic pathway in the destruction of cardiomyocytes, cellular inflammatory infiltration, and control of parasitaemia and mortality. We observed that although parasitaemia was equivalent in perforin (+/+) and (-/-) groups, survival rate and spontaneous physical performance were significantly lower in the perforin deficient mice. The cardiac inflammatory cell infiltration, mostly composed of CD8+ cells, was more evident in perforin (-/-) mice. Ultrastructural and immunofluorescence analysis, as well as plasma creatine kinase activity, revealed cardiomyocyte damage and necrosis, more evident in perforin (-/-) mice. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) assays performed in heart samples revealed similar and modest levels of apoptosis in both perforin (+/+) and (-/-) mice. These results indicate that perforin does not play a pivotal role in the control of parasitaemia and direct lysis of cardiomyocytes, but seems to be an important molecule involved in the control of cardiac inflammation and pathology induced by a highly virulent strain of T. cruzi.