Inhibition of Rho kinase by fasudil hydrochloride attenuates lung injury induced by intestinal ischemia and reperfusion

Aim: The aim of this study is to evaluate the role of Rho-kinase in the pathogenesis of lung injury induced by intestinal ischemia/reperfusion (I/R) and the preconditioning effects of fasudil hydrochloride. The novel therapeutic approach of using Rho-kinase inhibitors in the treatment of intestinal I/R is introduced. Methods: Sprague Dawley (SD) rats were divided into 4 groups: intestinal I/R group, two fasudil pretreatment groups (7.5 mg/kg and 15 mg/kg), and controls. Intestinal and lung histopathology was evaluated; myeloperoxidase (MPO) and superoxide dismutase (SOD) levels in lung parenchyma were determined. Serum tumor necrosis factor-a (TNF-alpha) and interleukin-6 (IL-6) were measured. eNOS and P-ERM expression were measured by Western Blot Results: Lung and intestinal injury were induced by intestinal I/R, characterized by histological damage and a significant increase in BALF protein. Compared to controls, serum TNF-alpha, IL-6, and lung MPO activity increased significantly in the I/R group, while SOD activity decreased. A strongly positive P-ERM expression was observed, while eNOS expression was weak. After fasudil administration, injury was ameliorated. Serum TNF-alpha, IL-6, lung MPO and P-ERM expression decreased significantly as compared to the I/R group, while SOD activity and eNOS expression increased significantly. Significance: Rho-kinase plays a key role in the pathogenesis of lung injury induced by intestinal I/R. The inhibition of the Rho-kinase pathway by fasudil hydrochloride may prevent lung injury. Crown Copyright (C) 2010 Published by Elsevier Inc. All rights reserved.