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Oxidative Medicine and Cellular Longevity
Volume 2018, Article ID 1240192, 13 pages
Research Article

Intermittent Hypoxia Increases the Severity of Bleomycin-Induced Lung Injury in Mice

1Laboratoire Hypoxie & Poumon (EA 2363), Université Paris 13, Sorbonne Paris Cité, 93017 Bobigny, France
2Hôpital Avicenne (AP-HP), 93009 Bobigny, France
3AP-HP, Hôpital Jean Verdier, 93140 Bondy, France
4UPMC, Sorbonne Université, 75013 Paris, France

Correspondence should be addressed to Carole Planès; rf.phpa@senalp.elorac

Received 26 July 2017; Revised 3 January 2018; Accepted 10 January 2018; Published 14 March 2018

Academic Editor: Jean-Louis Pepin

Copyright © 2018 Thomas Gille et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Background. Severe obstructive sleep apnea (OSA) with chronic intermittent hypoxia (IH) is common in idiopathic pulmonary fibrosis (IPF). Here, we evaluated the impact of IH on bleomycin- (BLM-) induced pulmonary fibrosis in mice. Methods. C57BL/6J mice received intratracheal BLM or saline and were exposed to IH (40 cycles/hour; FiO2 nadir: 6%; 8 hours/day) or intermittent air (IA). In the four experimental groups, we evaluated (i) survival; (ii) alveolar inflammation, pulmonary edema, lung oxidative stress, and antioxidant enzymes; (iii) lung cell apoptosis; and (iv) pulmonary fibrosis. Results. Survival at day 21 was lower in the BLM-IH group (). Pulmonary fibrosis was more severe at day 21 in BLM-IH mice, as assessed by lung collagen content () and histology. At day 4, BLM-IH mice developed a more severe neutrophilic alveolitis, (). Lung oxidative stress was observed, and superoxide dismutase and glutathione peroxidase expression was decreased in BLM-IH mice ( versus BLM-IA group). At day 8, pulmonary edema was observed and lung cell apoptosis was increased in the BLM-IH group. Conclusion. These results show that exposure to chronic IH increases mortality, lung inflammation, and lung fibrosis in BLM-treated mice. This study raises the question of the worsening impact of severe OSA in IPF patients.