Exogenous α-calcitonin gene-related peptide attenuates lipopolysaccharide-induced acute lung injury in rats
α-Calcitonin gene-related peptide (α-CGRP) is a 37 amino-acid neuropeptide that is primarily released from Ctype sensory neurons. αCGRP exerts multiple modulatory effects on immune responses and visceral organ function, but the role of exogenous αCGRP in lipopolysaccharide (LPS)induced acute lung injury (ALI) has remained to be elucidated. Fortyeight rats were randomized to receive continuous intraperitoneal infusion of αCGRP (0.4 µg/kg/min) or normal saline for 30 min, followed by intratracheal injection of 0.5 mg/kg LPS or saline. There were four groups of animals: The salinesaline (SS) group; the salineαCGRP (SC) group; the LPSsaline (LS) group and the LPSαCGRP (LC) group. Mean arterial pressure and arterial blood gases were assessed prior to αCGRP and LPS administration and every hour following LPS treatment. After 4 h, bronchoalveolar lavage was performed and used to assess total cell count and levels of tumor necrosis factorα, interleukin1β, intracellular cell adhesion molecule 1 and macrophage inflammatory protein 2. Lung tissue was also collected for assessing wettodry (W/D) ratio, histology and Evans blue (EB) dye extravasation. Pulmonary αCGRP concentration and αCGRP receptor expression were also examined, and inducible cyclic adenosine monophosphate early repressor (ICER) and TNFα mRNA expression levels were measured. Treatment with exogenous αCGRP improved oxygenation during LPSinduced ALI. Correspondingly, histological injury, total cell count, inflammatory cytokine levels, W/D ratio and EB dye extravasation were also significantly reduced. αCGRP receptor 1 expression was noted in pulmonary endothelial cells and alveolar macrophages and αCGRP receptor expression levels were decreased during ALI, whereas pulmonary αCGRP expression was continuously increased. Furthermore, exogenous αCGRP induced upregulation of ICER during LPSinduced ALI. In conclusion, exogenous αCGRP improved oxygenation and ameliorated lung damage in LPSinduced ALI, and these effects were associated with the upregulation of ICER.
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Document Type: Research Article
Affiliations: Department of Anesthesiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China
Publication date: August 1, 2015
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