Effects of aerobic physical training on the chronic allergic pulmonary inflammation in mice: role of purinergic signaling

Abstract

In the last years, a growing number of studies have demonstrated that the aerobic physical training (APT), performed in the proper intensity, duration and frequency, display several benefits to asthmatic patients, including improvement in quality of life, reduction in the levels of anxiety and depression, improvements in minute ventilation, reduction in the number of crisis, reduction in the levels of exhaled nitric oxide, beyond reduced daily needing of corticosteroids. More recently, was demonstrated for the first time that APT presents a direct anti-inflammatory effect on the airways of asthmatic patient, since that APT reduced the number of eosinophils in the induced sputum of these patients.However, several questions and hypothesis were raised up about the possible mechanism involved in these anti-inflammatory effects of APT for asthma. In this way, a growing number of experimental studies using models of asthma have been published, revealing possible mechanism involved of action APT for asthma. On the other side, until this moment no study evaluated the effects of APT on the via of purinergic receptors, a family of receptors that present a central role in the physiopathology of asthma. Therefore, the present study aims to evaluate if the anti-inflammatory effects of APT for asthma is mediate, at least partially, by the inhibition of expression of purinergic receptors, as well as by reduction in the levels of main agonist of purinergic receptor, the extracellular adenosine triphosphate (ATP).Thus, using 60 male C57Bl/6, divided in 4 experimental groups (Control, n = 20), (Exercise, n = 20), (Asthma, n = 20) and (Asthma + Exercise, n = 20). The experimental model of asthma (chronic pulmonary allergic inflammation) will be induced through the intra-peritoneal injection of ovalbumin solution on days 0 and 14, followed by inhalation of 1% ovalbumin, 3x/week, and beginning on 21st day until the 53rd day of experimental protocol. Aiming to evaluate the therapeutic effects of APT on the inflammation and on the via of purinergic receptors, the low intensity APT will be performed 5x/week, 60 min/session, begining on 27th day of experimental protocol until the 53rd day, when the airways inflammation is already established. Twenty-four hours after the last inhalation and training session, mice will be anesthetized, tracheotomized, canuled and the bronchoalveolar lavage will be collected and analyzed for the ATP levels and also the total number of cells as well as the differential number of cells. The analysis of respiratory mechanics and also the hyperresponsiveness will be performed. The histological analysis will be performed aiming to evaluate and quantify the number of lymphocytes and eosinophils in the airways wall, and also the airway remodeling. The expression of purinergic receptors (P2X7, P2Y2 and P2Y6) in the lung tissue homogenate will be performed using western blotting and also the Immunohistochemistry technique. (AU)