Document Type
Article
Publication Title
Respiratory Physiology & Neurobiology
Abstract
Obstructive sleep apnea (OSA) has been linked to increased mortality in pulmonary fibrosis. Its key feature, chronic intermittent hypoxia (CIH), can lead to oxidative stress and inflammation, known to lead to fibrotic pathology in other organs. We tested the effects of CIH in an animal model of bleomycin-induced lung fibrosis. Sprague Dawley rats were instilled intratracheally with bleomycin (Blm) or saline (Sal), and exposed to CIH or normal air (Norm) for 9 or 30 days. Pulmonary function was tested and lungs were harvested for histological and molecular analyses. In Blm-treated animals, 30days of CIH compared to Norm increased total lung collagen content (p=0.008) and reduced Quasi-static lung compliance (p=0.04). CIH upregulated lipid peroxidation and increased NF-κB activation, IL-17 mRNA and Col1α1 mRNA expression. Our results indicate that following Blm-induced lung injury, CIH amplifies collagen deposition via oxidative and inflammatory pathways, culminating in stiffer lungs. Thus, OSA may augment fibrosis in patients with interstitial lung disease.
DOI
10.1016/j.resp.2017.04.010
Publication Date
10-2018
Keywords
Fibrosis, Hypoxia, Intermittent, Lung/immunology/metabolism/pathology, Obstructive, Sleep apnea
ISSN
1878-1519
Recommended Citation
Braun RK, Broytman O, Braun FM, Brinkman JA, Clithero A, Modi D, Pegelow DF, Eldridge M, Teodorescu M. Chronic Intermittent Hypoxia Worsens Bleomycin-Induced Lung Fibrosis in Rats. Respiratory Physiology & Neurobiology. 2018; 256. doi: 10.1016/j.resp.2017.04.010.
