Estudo morfo-funcional do pulmão em modelo de enfisema induzido por elastase em camundongos

Abstract

The chronic obstructive pulmonay disease (COPD) is a major cause of death and disability worldwide. It is a public health problem and the pathophysiology needs to be better elucidated. Therefore, the present study aimed to develop models of pancreatic elastase-induced emphysema (PPE) in an attempt to obtain lung functional and morphological changes that resemble human emphysema and, thus, improve the understanding of its pathophysiology. Thirty-sixs Swiss male mice (25-30g) were randomly divided into control group and emphysema. The control group (subdivided into Sal x 1 and Sal x 2) received intratracheal instillation of saline while emphysema group (subdivided into 0,3 U x 1, 0,3 U x 2, 0,6 U x 1, 0,6 U x 2) received intratracheal instillation of elastase 0,3 U or 0,6 U, single (x1) and double (x2). Twenty days after the first instillation, all animals were sedated, anesthetized and paralyzed. Lung mechanical parameters: resistive pressure (ΔP1,L), viscoelastic (ΔP2,L) and elastance (Est, L) were measured by end-inflation occlusion method. Lungs were prepared for analysis of morphometry and quantification of elastic and collagen fibers in lung tissue. The pulmonary exposure to PPE led to functional changes in 0.3U x 2 group by reducing the elastic recoil; lung morphological modifications by increasing the mean linear intercept in 0,6U x 1 and 0,3U x 2 groups; increased of inflammatory cells influx in the lung parenchyma and reduced of elastic fiber content in alveolar septa in all groups, and increased collagen fiber deposition in 0,6U x 1 and 0,6U x 2 groups. In conclusion, all developed elastase induced-emphysema models in the present study presented morphological changes similar to those found in human emphysema, but only 0.3 U x 2 group showed functional and morphological changes.