1. Inhibition of Rho kinase by fasudil hydrochloride attenuates lung injury induced by intestinal ischemia and reperfusion.
- Author
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Li Y, Yao JH, Hu XW, Fan Z, Huang L, Jing HR, Liu KX, and Tian XF
- Subjects
- 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine pharmacology, Acute Lung Injury etiology, Acute Lung Injury physiopathology, Animals, Interleukin-6 analysis, Intestines chemistry, Intestines enzymology, Intestines pathology, Ischemia complications, Lung chemistry, Lung enzymology, Lung pathology, Male, Nitric Oxide Synthase Type III metabolism, Peroxidase metabolism, Rats, Rats, Sprague-Dawley, Reperfusion Injury metabolism, Reperfusion Injury physiopathology, Superoxide Dismutase metabolism, Tumor Necrosis Factor-alpha analysis, 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine analogs & derivatives, Acute Lung Injury drug therapy, Intestines blood supply, Ischemia physiopathology, Reperfusion Injury drug therapy, rho-Associated Kinases antagonists & inhibitors
- Abstract
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-α (TNF-α) 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-α, 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-α, 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 © 2010. Published by Elsevier Inc. All rights reserved.)
- Published
- 2011
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