Avaliação experimental da responsividade das vias aéreas em camundongos após indução do enfisema pulmonar por elastase

Abstract

Chronic Obstructive Pulmonary Disease (COPD) is a disease that presents airflow obstruction. In emphysema, there is destruction of the extracellular matrix resulting in enlargement of the airspace. The bronchial hyperresponsiveness can occur in patients with COPD. In this context, the objective of this study was to evaluate the responsiveness after bronchial challenge with methacholine (MCh) in a model of emphysema induced by porcine pancreatic elastase (PPE). Swiss male mice (25 - 30g) were randomly divided into three groups: the control group was intratracheally instilled with saline and emphysema group was subdivided into two other groups that were instilled with PPE (0.3 and 0.6 U). After 20 days the animals were anesthetized , tracheotomized , connected to ventilator for small animals and subjected to inhalation of salina and MCh (50 and 100mg/mL) . The evaluation of respiratory mechanics used the model of constant phase and the parameters analyzed were airway resistance (Raw), tissue resistance (G), tissue elastance (H) and hysteresivity (ç). The lungs were removed for histological analysis and quantification of proteins after the test. The results of respiratory mechanics showed that the baseline and after nebulization with saline the parameters Raw, G and ç showed no differences between groups when compared with the control group, but the H in group emphysema 0.6U was lower . After challenge with MCh 100mg/mL Raw was attenuated in animals with emphysema 0.3U. The G increased in animals with emphysema 0.3U. The H in animals with emphysema 0.6 U decreased. The ç after misting of MCh 50 and 100mg/mL increased in animals instilled with PPE 0.3 and 0.6U. In the morphological analysis the group treated with PPE 0.6U increased areas of alveolar collapse, alveolar number of hyperinflation was higher in groups emphysema 0.3 and 0.6U, linear mean intercept increased in both groups treated with PPE and reduced number of normal alveoli in both groups emphysema when compared with the control group. The protein quantification showed decrease of elastin in the group 0.6 U and increased collagen type III in the groups treated with PPE. Our results show that animals with elastase-induced emphysema 0.3U have attenuation of bronchial hyperresponsiveness during inhalation of MCh (100mg/mL), suggesting that loss of integrity of the epithelial lung tissue and tissue remodeling increased the heterogeneity of lungs.