Avaliação morfológica da aorta em modelo knockout mgΔ LoxPneo na linhagem 129/Sv da síndrome de Marfan

• Ano de defesa: 2016
• Autor(a) principal: Souza, Rodrigo Barbosa de [UNIFESP]
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Marfan syndrome; Aneurysm; Extracellular matrix; Microscopy; Enzyme immunoadsorption assay; Síndrome de Marfan; Aneurisma; Matrix extracelular; Microscopia; Ensaio de imunoadsorção enzimática
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=4060351; http://repositorio.unifesp.br/handle/11600/47238

Marfan syndrome (MPS) is a dominant autosomal disease with gene mutations encoding fibrillin-1 protein, a constituent of elastic fibers systems widely distributed in the extracellular matrix, thus promoting skeletal ocular and vascular disorders. Vascular alterations have been associated with SMF mortality, however the pathogenesis has not been fully elucidated requiring the need for research with animal models. The aim of this study was to evaluate the vascular phenotype in mg?LoxPneo 129 / Sv model. Method: 29 female mice were evaluated: 24 affected and five normal. Six month old animals were submitted to the study of the thoracic aorta concerning to morphology, qualitative and quantitative vascular phenotypes and serum TGF?1. The 6 fragments of the thoracic aorta between the TI-TVIII segments were fixed in glutaraldehyde 2.5% and buffered, and then were evaluated by light microscopy (5 fragments included in historesin Technovit 7100® and stained by techniques: Toluidine Blue borated 1% ; hematoxylin and eosin, Resorcinol-Fuchsin Weigert, Sirius Red, and osmic acid to fat) and by transmission electronic microscopy (01 segment included in Spurr® resin). The images were evaluated in Carl-Zeiss Axio Scope A1® and PHILIPS IN 208S® operated at 80 kV coupled to Axiovision 4.8® software, respectively. Result: Animals with SMF showed marked thoracic lordosis in TI-TVIII segment associated with deformities of the thoracic aorta. In SMF group, 18/24 animals showed vascular diseases (15 aneurysm, 6 classic dissection, 1 aortic ulcer and intramural hematoma 1) and 5/18 with multiple aneurysms and 6/18 with multiple vascular diseases. In addition, 100% of the SMF animals showed the fragility of the tunica adventitia, collagen type III in the classic dissections and fragmented collagen fibers in aneurysms. In 95% of SMF animals was observed endothelium cells vacuolization and also in the tunica media, which by osmic acid technique for fat showed that the vacuoles of the tunica media were of lipids. Conclusion: The model mg?LoxPneo 129 / Sv showed similar vascular alterations seen in the clinical SMF, suggesting a suitable experimental model for the study of SMF.