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BioMed Research International
Volume 2017 (2017), Article ID 8314276, 9 pages
https://doi.org/10.1155/2017/8314276
Research Article

Simvastatin Ameliorates PAK4 Inhibitor-Induced Gut and Lung Injury

1Emergency Department, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
2Emergency Department, Shanghai Tenth People’s Hospital, Shanghai 200072, China

Correspondence should be addressed to Chengjin Gao; moc.361@3002oagnijgnehc

Received 30 July 2017; Accepted 29 November 2017; Published 28 December 2017

Academic Editor: Anjali Joshi

Copyright © 2017 Shuming Pan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

P21 activated kinase 4 (PAK4), a key regulator of cytoskeletal rearrangement and endothelial microparticles (EMPs), is released after lipopolysaccharide (LPS) stimulation. In addition, it participates in LPS-induced lung injury. In this study, forty-eight Sprague Dawley (SD) rats were divided into two groups, including PAK4 inhibitor (P) and PAK4 inhibitor + simvastatin (P + S) treatment groups. All rats were given PAK4 inhibitor (15 mg/kg/d) orally. Immediately after PAK4 inhibitor administration, simvastatin was injected intraperitoneally to P + S group animals at 20 mg/kg/day. Then, treatment effects on the intestinal mucosal barrier and lung injury caused by PAK4 inhibitor and simvastatin were assessed. The results showed that gut Zonula Occludens- (ZO-) 1, PAK4, mitogen-activated protein kinase 4 (MPAK4), and CD11c protein levels were reduced, while plasma endotoxin levels were increased after administration of PAK4 inhibitor. Furthermore, compared with normal rats, wet-to-dry (W/D) values of lung tissues and circulating EMP levels were increased in the treatment group, while PAK4 and CD11c protein amounts were reduced. Therefore, in this lung injury process induced by PAK4 inhibitor, the protective effects of simvastatin were reflected by intestinal mucosal barrier protection, inflammatory response regulation via CD11c+ cells, and cytoskeleton stabilization. In summary, PAK4 is a key regulator in the pathophysiological process of acute lung injury (ALI) and can be a useful target for ALI treatment.