01 April 2010
Fasudil attenuates lipopolysaccharide-induced acute lung injury in mice through the Rho/Rho kinase pathway
Yan LiABCDEF, Yiling WuADG, Zhi WangAEF, Xuan-hong ZhangAEF, Wei-kang WuABCDEFGMed Sci Monit 2010; 16(4): BR112-118 :: ID: 878494
Abstract
Background
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.
Results
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.
Conclusions
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, Lung - enzymology, Lipopolysaccharides - toxicity, Gene Expression Regulation, Enzymologic, Endothelium, Vascular - pathology, RNA, Messenger - metabolism, Bronchoalveolar Lavage, 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine - pharmacology, rho GTP-Binding Proteins - metabolism, rho-Associated Kinases - metabolism
Editorial
01 April 2024 : Editorial
Editorial: Forty Years of Waiting for Prevention and Cure of HIV Infection – Ongoing Challenges and Hopes for Vaccine Development and Overcoming Antiretroviral Drug ResistanceDOI: 10.12659/MSM.944600
Med Sci Monit 2024; 30:e944600
In Press
07 Mar 2024 : Clinical Research
Knowledge of and Attitudes Toward Clinical Trials: A Questionnaire-Based Study of 179 Male Third- and Fourt...Med Sci Monit In Press; DOI: 10.12659/MSM.943468
08 Mar 2024 : Animal Research
Modification of Experimental Model of Necrotizing Enterocolitis (NEC) in Rat Pups by Single Exposure to Hyp...Med Sci Monit In Press; DOI: 10.12659/MSM.943443
18 Apr 2024 : Clinical Research
Comparative Analysis of Open and Closed Sphincterotomy for the Treatment of Chronic Anal Fissure: Safety an...Med Sci Monit In Press; DOI: 10.12659/MSM.944127
08 Mar 2024 : Laboratory Research
Evaluation of Retentive Strength of 50 Endodontically-Treated Single-Rooted Mandibular Second Premolars Res...Med Sci Monit In Press; DOI: 10.12659/MSM.944110
Most Viewed Current Articles
17 Jan 2024 : Review article
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
14 Dec 2022 : Clinical Research
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
16 May 2023 : Clinical Research
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952