01 April 2010
Fasudil attenuates lipopolysaccharide-induced acute lung injury in mice through the Rho/Rho kinase pathwayYan LiABCDEF, Yiling WuADG, Zhi WangAEF, Xuan-hong ZhangAEF, Wei-kang WuABCDEFG
Med Sci Monit 2010; 16(4): BR112-118 :: ID: 878494
The transendothelial migration of polymorphonuclear leukocytes (PMNs, neutrophils) may be a hallmark of acute lung injury (ALI). The breakdown of the vascular endothelial barrier has likewise been considered to have etiologic linkage in the pathogenesis of ALI. Rho-associated coiled-coil-forming protein kinase (ROCK), a downstream target effector of the small GTP-binding protein Rho, plays a key role in cell adhesion, motility, and contraction mediated by reorganization of the actin cytoskeleton. The aims were to investigate protection by fasudil in lipopolysaccharide (LPS)-induced ALI and the role of ROCK2 in neutrophil transendothelial migration in a murine model.
Material and Method
Mice were assigned to three groups: sham-treated controls (Sham group), LPS instillation (LPS group), and protective application of fasudil and LPS instillation (Fasudil/LPS group). Indexes tested were breathing frequency, histopathological examination, lung injury score, lung wet-to-dry weight ratio, neutrophil percentage in bronchoalveolar lavage fluid (BALF), myeloperoxidase activity, and ROCK2 mRNA expression in lung homogenate.
Permeability pulmonary edema (histopathological examination, lung injury score, and lung wet-to-dry weight ratio) was ameliorated and neutrophil infiltration in the lungs (neutrophil percentage in BALF, myeloperoxidase activity) was depressed in response to fasudil administration. Expression of ROCK2 mRNA in the lung homogenates of the LPS-treated mice increased approximately fourfold; however, fasudil did not affect the increase.
The Rho/Rho kinase pathway may play an important role in the pathogenesis of LPS-induced ALI and fasudil, as a ROCK inhibitor, could decrease neutrophil transendothelial migration by attenuating cytoskeletal rearrangement of endothelial cells, leading to the inhibition of ALI development.
Keywords: Protein Kinase Inhibitors - pharmacology, Organ Size, Neutrophils - metabolism, Mice, Inbred C57BL, Lung - enzymology, Lipopolysaccharides - toxicity, Gene Expression Regulation, Enzymologic, Endothelium, Vascular - pathology, RNA, Messenger - metabolism, Cell Movement, Bronchoalveolar Lavage, 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - pharmacology, rho GTP-Binding Proteins - metabolism, rho-Associated Kinases - metabolism
01 August 2022 : EditorialEditorial: Long-Term Effects of Symptomatic and Asymptomatic SARS-CoV-2 Infection in Children and the Changing Pathogenesis of Common Childhood Viruses Driven by the COVID-19 Pandemic
Med Sci Monit 2022; 28:e937927
12 Aug 2022 : Clinical ResearchRisk Factors and Pathogen Spectrum in Continuous Ambulatory Peritoneal Dialysis-Associated Peritonitis: A S...
Med Sci Monit In Press; DOI: 10.12659/MSM.937112
11 Aug 2022 : Meta-AnalysisOptimal Surgical Treatment Method for Anterior Cruciate Ligament Rupture: Results from a Network Meta-Analysis
Med Sci Monit In Press; DOI: 10.12659/MSM.937118
10 Aug 2022 : Review articleProgrammed Cell Death in Diabetic Nephropathy: A Review of Apoptosis, Autophagy, and Necroptosis
Med Sci Monit In Press; DOI: 10.12659/MSM.937766
Most Viewed Current Articles
30 Dec 2021 : Clinical ResearchRetrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis o...
Med Sci Monit 2021; 27:e935379
13 Nov 2021 : Clinical ResearchAcceptance of COVID-19 Vaccination and Its Associated Factors Among Cancer Patients Attending the Oncology ...
Med Sci Monit 2021; 27:e932788
08 Mar 2022 : Review articleA Review of the Potential Roles of Antioxidant and Anti-Inflammatory Pharmacological Approaches for the Man...
Med Sci Monit 2022; 28:e936292