MAPPING OF DIFFERENT TYPES OF NICOTIN RECEPTORS ALONG THE LUNGS OF ANIMALS WITH ACUTE PULMONARY INJURY

Abstract

The Acute Respiratory Distress Syndrome (ARDS) is defined as a severe lung diseasethat can lead to respiratory failure. Among the main causes is bacterial and/or viralpneumonia. The inflammatory process and cytokine storm is the mainpathophysiological characteristic and can compromise lung function and other organs.Several mechanisms and mediators are described as important in the pathophysiology ofARDS, including the anti-inflammatory cholinergic system, which can act byattenuating the inflammatory process. Activation of the nicotinic acetylcholinereceptor, in particular alpha-7, has seemed promising in attenuating the inflammatoryresponse in experimental models. However, little is known about the participation ofother types of nicotinic receptors in the acute pulmonary inflammatory response.Objective: To map the expression of nicotinic receptors alpha-3, alpha-4, alpha-7, beta-2e beta-4 (nicotinic acetylcholine receptors) nAChR in the lung, in a model of acute lunginjury. Methodology: Male C57 mice will be divided into 3 groups: control, which willreceive intratracheal instillation with saline; the experimental group that will receiveintratracheal LPS instillation, and the group that will receive intratracheal LPSinstillation and will be treated with therapeutic PNU 282987. The animals will beeuthanized 24 hours after LPS instillation. Histological sections of the lung will beperformed, evaluation of pulmonary edema through dry weight, wet weight, index ofdistension and collapse and inflammation. In addition, immunohistochemistry will beperformed to detect alpha-3, alpha-4, alpha-7, beta-2 e beta-4 nAChR expression inairways and lung parenchyma. Immunofluorescence will also be performed to detectnAChR associated with (vesicular acetylcholine transporter protein) VAChT and/ormacrophages, by double labeling. Statistical analysis will be performed by One-WayANOVA using the Graph-Prisma Program and results with p<0.05 will be consideredsignificant. It is expected that acute inflammation, as well as activation of alpha-7nAChR receptors, which is associated with reduced inflammation, modulate nAChRexpression. It also aims to clarify whether, in this model, the nAChRs that eventuallychange their expression are neuronal or non-neuronal. Elucidating the participation ofother types of nAChR in the inflammatory response may expand other therapeutictargets for the treatment of ARDS.