Abstract
Background: Intestinal ischemia-reperfusion (II/R) can lead to indirect lung injury. Previous studies have shown that p38 kinase may be involved in acute lung injury (ALI). However, the exact role of p38 mitogen-activated protein kinase (MAPK) and possible mechanisms in lungs are unknown and no specific treatment exists for II/R-induced ALI. The purpose of this study was to investigate the protective role of p38 MAPK inhibition in the regulation of the inflammatory response to ALI induced by II/R in rats.Methods: II/R was induced by occlusion of the superior mesenteric artery (SMA) and coeliac artery (CA) for 40 minutes and subsequent reperfusion for 0, 8, 16, 24 hours. SB239063, a specific inhibitor of p38 MAPK, was injected (10 mg/kg) intraperitoneally 60 minutes before the operation. The severity of ALI was measured by histology analysis (hematoxylin-eosin [HE] staining and ALI scoring) and lung edema (lung wet/dry weight ratio). Quantitative polymerase chain reaction (qPCR), western blot (WB), and immunofluorescent staining were employed to assess expression and location of interleukin-6 (IL-6) and p38 MAPK, respectively.Results: ALI including lung edema, alveolar collapse, hemorrhage, exudation and infiltration of inflammatory cells in the lungs was induced by II/R and expression levels of IL-6 and p38 MAPK protein in the lung tissues were significantly increased at 8 and 16 hours after reperfusion, respectively compared with that in the sham group. SB239063 administration significantly down-regulated p38 MAPK and IL-6 concentration in the lung specimens, therefore, protected effectively lung tissues from injury after II/R.Conclusions: These findings indicated that p38 MAPK inhibition may downregulate the expression of IL-6 to protect lung from ALI induced by II/R, which could be used as a potential target for the prevention or treatment of ALI caused by II/R. Citation: Liu-Lin Xiong, Yun-Xia Zuo, Chao-Zhi Luo, Jie Yu, Qing-Jie Xia, Fei-Fei Xu, et al. p38 MAPK inhibitor administration provides protection against acute lung injury in rats with intestinal ischemia reperfusion via downregulating interlukin-6 expression. J Anesth Perioper Med 2016; 3: 27-34. doi: 10.24015/JAPM.2016.0004This is an open-access article, published by Evidence Based Communications (EBC). This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium or format for any lawful purpose. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
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