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Doctoral Thesis
DOI
10.11606/T.17.2009.tde-12012010-192629
Document
Author
Full name
Cristina Tonin Beneli
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2009
Supervisor
Committee
Ramos, Simone Gusmão (President)
Metze, Konradin
Oliveira, Jose Alberto Mello de
Pasqualucci, Carlos Augusto Goncalves
Piccinato, Carlos Eli
Title in Portuguese
Estudo da participação das metaloproteinases 2 e 9 no desenvolvimento da hiperplasia intimal decorrente de modelo experimental de estenose intrínseca da aorta
Keywords in Portuguese
Estenose intrínseca da aorta
Hiperplasia intimal
Metaloproteinase-2
Metaloproteinase-9
Abstract in Portuguese
As metaloproteinases têm sido implicadas no desenvolvimento de hiperplasias intimais em diferentes situações. O objetivo do presente trabalho foi avaliar a participação das metaloproteinases 2 e 9 no desenvolvimento da hiperplasia intimal decorrente de modelo experimental de estenose intrínseca da aorta. Este modelo consiste na inserção de um pino acrílico na aorta de ratos. Foram utilizados 288 ratos Wistar machos, com peso médio de 250 g, os quais foram separados em quatro grupos: (1) controle sham-operado, (2) controle sham-operado tratado com doxiciclina, (3) estenosado e (4) estenosado tratado com doxiciclina. Estes animais foram tratados com doxiciclina (inibidor não-seletivo de metaloproteinases) 30 mg/Kg/dia e sacrificados nos períodos de 1, 7, e 15 dias após a cirurgia. O segmento da aorta envolvendo o pino foi retirado e estudado com diferentes protocolos para: microscopia óptica de alta resolução e convencional, imunoistoquímica, Western blot para eNOS e iNOS, zimografia convencional e in situ. Um trombo se formou ao redor do pino 24 horas após a cirurgia, mostrando sinais de organização com 7 dias. Com 15 dias, uma hiperplasia intimal adjacente à base do pino foi visualizada. Este espessamento foi caracterizado principalmente por células musculares lisas provenientes da camada muscular média. Apesar das metaloproteinases 2 e 9 estarem inibidas pela doxiciclina (comprovado pela imunoistoquímica, zimografia convencional e in situ), não observamos alterações importantes na composição e desenvolvimento da hiperplasia intimal decorrente deste modelo experimental de estenose intrínseca da aorta
Title in English
Study of the Participation of metalloproteinases 2 and 9 in development of intimal hyperplasia due to experimental model of intrinsic aorta stenosis
Keywords in English
Intimal hyperplasia
Intrinsic aorta stenosis
Metalloproteinases-2
Metalloproteinases-9
Abstract in English
Metaloproteinases has been implied in the development of intimal hyperplasia in different situations. We have used an experimental model of aorta stenosis, with a mushroom plug that promotes local turbulence and thrombosis. Methods: 288 Wistar male rats, weighing an average of 250g, were allocated into four groups: control groups, sham-operated and sham-operated treated with doxycycline, and experimental groups, operated and operates treated with doxycycline. The animals were killed on days 1, 7, and 15 after surgery. The fragments of aorta implicating the plug were harvested and studied using high resolution light microcopy, immunohistochemistry, Western Blot to eNOS and iNOS, conventional and in situ zymography. With animal survival of more than 24 h, we followed the partial fibrinolysis of the thrombus as well as its posterior organization and incorporation to the arterial wall as a neointima for up to 15 days. The intimal thickening detected was mainly composed of smooth muscle cells migrated from the medial layer of the aorta intermixed with extracellular matrix. Although, the MMP-2 and 9 were inhibiting, the intimal hyperplasia did not show difference in your composition and development.
 
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DOUTORADO.pdf (4.29 Mbytes)
Publishing Date
2015-05-25
 
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