• Hong-Bin Li, Guang-Zhi Wang, Jie Gong, Zhou-Yang Wu, Si Guo, Bo Li, Mei Liu, Yu-Dong Ji, Min Tang, Shi-Ying Yuan, You Shang, and Shang-Long Yao.
• Department of Critical Care Medicine, Institute of Anesthesia and Critical Care, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
• J. Surg. Res. 2013 Aug 1;183(2):710-9.

BackgroundHemorrhagic shock activates cellular stress signals and can lead to systemic inflammatory response, organ injury, and death. Mitogen-activated protein kinase (MAPK) acts as a sensor of tissue injury in models of ischemia-reperfusion injury. Lipoxins are endogenous lipid mediators with potent anti-inflammatory and pro-resolving actions. We hypothesized that BML-111 (a lipoxin A4-receptor agonist) attenuates hemorrhagic shock-induced acute lung injury (ALI) through inhibiting activation of the MAPK pathway.MethodsWe randomized Sprague-Dawley rats into four groups: sham, hemorrhagic shock-resuscitation (HS), HS plus BML-111 (BML-111), and HS plus BML-111 and BOC-2 (BOC-2). Two hours after resuscitation, we collected samples of lung. We obtained bronchoalveolar lavage fluid for neutrophil count. We performed optical microscopy to examine pathologic changes in lungs. Wet/dry ratios, myeloperoxidase expression, interleukin (IL)-1β and IL-6 levels in lung were measured. We evaluated MAPK activation and the DNA binding activity of activator protein-1 in lung.ResultsTreatment with BML-111 reduced the lung damage and wet/dry ratio, neutrophil count in bronchoalveolar lavage fluid, expression of myeloperoxidase, and production of IL-1β and IL-6 in lung. Phosphorylation of MAPK was also decreased by BML-111 in lung. Furthermore, the DNA binding activity of activator protein-1 was blocked by BML-111. An antagonist of the lipoxin A4-receptor, BOC-2, reversed the protective effect of BML-111 on ALI induced by hemorrhagic shock.ConclusionsThis study indicates that BML-111 attenuated hemorrhagic shock-induced ALI via the MAPK/activator protein-1 signaling pathway. Therefore, BML-111 may have therapeutic potential for hemorrhagic shock-induced ALI.Copyright © 2013 Elsevier Inc. All rights reserved.

41 keywords...

hide…