title: Growth hormone releasing peptide-2, a ghrelin agonist, attenuates lipopolysaccharide-induced acute lung injury in rats.
abstract: Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), are the most common complications of sepsis, and the mortality of sepsis-induced ALI remains high in critically ill patients. Growth hormone releasing peptide-2 (GHRP-2), a ghrelin agonist, has been shown to exert beneficial effects on various inflammatory diseases. We therefore explored whether GHRP-2 possesses anti-inflammatory properties in the pathogenesis of lipopolysaccharide (LPS)-induced ALI. Male Sprague-Dawley rats were intratracheally instilled with LPS (2 mg/kg) to induce ALI. ALI was confirmed with lung tissue injury (histopathological examination), enhanced lung edema (wet-to-dry weight ratio), and neutrophil infiltration (myeloperoxidase activity) at 6 h after LPS exposure. The analyses of bronchoalveolar lavage fluid showed the significant increases in pulmonary permeability (total cells and protein) and the levels of proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). In contrast, these lung injury indexes were attenuated in rats that received a subcutaneous injection of GHRP-2 (100 microg/kg) 0.5 h prior to LPS administration. To further explore the potential anti-inflammatory mechanism of GHRP-2 in LPS-induced ALI, we assessed of nuclear factor-kappaB (NF-kappaB) activity in lung tissues at 6 h after LPS challenge. We thus found that pretreatment with GHRP-2 markedly suppressed the activation of NF-kappaB in lung tissues. These results indicate that GHRP-2 attenuated LPS-induced ALI. Early protection appears to be mediated partly through the inhibition of NF-kappaB pathway activation. The present study indicates that GHRP-2 acts as a potential therapeutic reagent for treating ALI.
authors.affiliation: Department of Anesthesia, Critical Care Medicine & Emergency Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan, Hubei Province, PR China.
authors.forename: Guang
authors.initials: G
authors.lastname: Li
authors.forename: Jianguo
authors.initials: J
authors.lastname: Li
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhou
authors.forename: Xuemin
authors.initials: X
authors.lastname: Song
authors.forename: Hui
authors.initials: H
authors.lastname: Liang
authors.forename: Lili
authors.initials: L
authors.lastname: Huang
mesh_terms: D055371:Acute Lung Injury / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D054439:Ghrelin / Q000819:agonists*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology / Q000627:therapeutic use*; D009195:Peroxidase / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D054439:Ghrelin; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009842:Oligopeptides; C091874:growth hormone-releasing peptide-2; D009195:Peroxidase