Xiu-Jie Qi1, Wei Ning2, Feng Xu3, Hong-Xing Dang3, Fang Fang4, Jing Li3. 1. Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Children's Hospital of Chongqing Medical University Chongqing 400014, China ; Department of Pediatric Intensive Care Unit, Children's Hospital of Chongqing Medical University Chongqing 400014, China. 2. Daping Hospital and The Research Institute of Surgery of The Third Military Medical University Chongqing 400042, China. 3. Department of Pediatric Intensive Care Unit, Children's Hospital of Chongqing Medical University Chongqing 400014, China. 4. Ministry of Education Key Laboratory of Child Development and Disorders, Key Laboratory of Pediatrics in Chongqing, Chongqing International Science and Technology Cooperation Center for Child Development and Disorders, Children's Hospital of Chongqing Medical University Chongqing 400014, China.
Abstract
BACKGROUND: Oxygen therapy is important during the management of high-risk neonatal infants, such as those with preterm birth, low birth weight, and asphyxia. However, prolonged exposure to high oxygen concentrations can readily lead to diffuse nonspecific inflammation, which promotes airway remodeling and pulmonary fibrosis. The Rho/Rho-associated coiled-coil kinase (Rho/ROCK) signaling pathway plays an important role in numerous developmental and proliferative diseases. This study was performed to determine the efficacy of ROCK inhibitor fasudil in blocking the development of hyperoxia-induced lung injury and fibrosis in neonatal rats. METHODS: Neonatal rats were randomly divided into four groups: air + saline group, air + fasudil group, hyperoxia + saline group, and hyperoxia + fasudil group. The hyperoxia + saline and Hyp + fasudil groups were exposed to 95% oxygen for 21 days and administered intraperitoneal saline or fasudil once daily. The air + saline and air + fasudil group were exposed to 21% oxygen (room air) and administered the same volume of intraperitoneal saline or fasudil. RESULTS: Fasudil-treated rats exhibited improved histopathological changes and decreased lung hydroxyproline content. Fasudil attenuated the protein level of alpha-smooth muscle actin, transforming growth factor-β1, and connective tissue growth factor. Additionally, fasudil reduced the activation of ROCK1 and myosin phosphatase targeting subunit 1 protein in the Rho/ROCK signaling pathway. CONCLUSIONS: Fasudil may be a potentially effective therapeutic drug for hyperoxia-induced pulmonary fibrosis.
BACKGROUND:Oxygen therapy is important during the management of high-risk neonatal infants, such as those with preterm birth, low birth weight, and asphyxia. However, prolonged exposure to high oxygen concentrations can readily lead to diffuse nonspecific inflammation, which promotes airway remodeling and pulmonary fibrosis. The Rho/Rho-associated coiled-coil kinase (Rho/ROCK) signaling pathway plays an important role in numerous developmental and proliferative diseases. This study was performed to determine the efficacy of ROCK inhibitor fasudil in blocking the development of hyperoxia-induced lung injury and fibrosis in neonatal rats. METHODS: Neonatal rats were randomly divided into four groups: air + saline group, air + fasudil group, hyperoxia + saline group, and hyperoxia + fasudil group. The hyperoxia + saline and Hyp + fasudil groups were exposed to 95% oxygen for 21 days and administered intraperitoneal saline or fasudil once daily. The air + saline and air + fasudil group were exposed to 21% oxygen (room air) and administered the same volume of intraperitoneal saline or fasudil. RESULTS:Fasudil-treated rats exhibited improved histopathological changes and decreased lung hydroxyproline content. Fasudil attenuated the protein level of alpha-smooth muscle actin, transforming growth factor-β1, and connective tissue growth factor. Additionally, fasudil reduced the activation of ROCK1 and myosin phosphatase targeting subunit 1 protein in the Rho/ROCK signaling pathway. CONCLUSIONS:Fasudil may be a potentially effective therapeutic drug for hyperoxia-induced pulmonary fibrosis.
Authors: Rebecca Lee; Charles Reese; Michael Bonner; Elena Tourkina; Zoltan Hajdu; Ellen C Riemer; Richard M Silver; Richard P Visconti; Stanley Hoffman Journal: Am J Physiol Lung Cell Mol Physiol Date: 2014-02-28 Impact factor: 5.464
Authors: Charles Reese; Rebecca Lee; Michael Bonner; Beth Perry; Jonathan Heywood; Richard M Silver; Elena Tourkina; Richard P Visconti; Stanley Hoffman Journal: Front Pharmacol Date: 2014-06-16 Impact factor: 5.810