Lipopolysaccharide-induced endotoxemia in corn oil-preloaded mice causes an extended course of lung injury and repair and pulmonary fibrosis: A translational mouse model of acute respiratory distress syndrome.
Acute respiratory distress syndrome (ARDS) is characterized by acute hypoxemia respiratory failure, bilateral pulmonary infiltrates, and pulmonary edema of non-cardiac origin. Effective treatments for ARDS patients may arise from experimental studies with translational mouse models of this disease that aim to delineate the mechanisms underlying the disease pathogenesis. Mouse models of ARDS, however, can be limited by their rapid progression from injured to recovery state, which is in contrast to the course of ARDS in humans. Furthermore, current mouse models of ARDS do not recapitulate certain prominent aspects of the pathogenesis of ARDS in humans. In this study, we developed an improved endotoxemic mouse model of ARDS resembling many features of clinical ARDS including extended courses of injury and recovery as well as development of fibrosis following i.p. injection of lipopolysaccharide (LPS) to corn oil-preloaded mice. Compared with mice receiving LPS alone, those receiving corn oil and LPS exhibited extended course of lung injury and repair that occurred over a period of >2 weeks instead of 3-5days. Importantly, LPS challenge of corn oil-preloaded mice resulted in pulmonary fibrosis during the repair phase as often seen in ARDS patients. In summary, this simple novel mouse model of ARDS could represent a valuable experimental tool to elucidate mechanisms that regulate lung injury and repair in ARDS patients.
Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois, United States of America.|Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, Illinois, United States of America.|Department of Pulmonary Disease, Qingpu Branch of Zhongshan Hospital, Fudan University, Shanghai, China.
Chaomin
C
Wu
Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois, United States of America.|Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, Illinois, United States of America.|Department of Physiology, Development and Neuroscience, School of Biological Sciences, University of Cambridge, Cambridge, United Kingdom.
Colin E
CE
Evans
Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois, United States of America.|Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, Illinois, United States of America.
Zhiyu
Z
Dai
Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois, United States of America.|Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, Illinois, United States of America.
Xiaojia
X
Huang
Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois, United States of America.|Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, Illinois, United States of America.
Xianming
X
Zhang
Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois, United States of America.|Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, Illinois, United States of America.
Hua
H
Jin
Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois, United States of America.|Department of Anesthesiology, University of Illinois College of Medicine, Chicago, Illinois, United States of America.
Guochang
G
Hu
Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China.
Yuanlin
Y
Song
Department of Pharmacology, University of Illinois College of Medicine, Chicago, Illinois, United States of America.|Center for Lung and Vascular Biology, University of Illinois College of Medicine, Chicago, Illinois, United States of America.
You-Yang
YY
Zhao
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003314:Corn Oil / Q000494:pharmacology; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000150:complications / Q000209:etiology*; D005260:Female; D008070:Lipopolysaccharides / Q000494:pharmacology*; D055370:Lung Injury / Q000139:chemically induced*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011658:Pulmonary Fibrosis / Q000139:chemically induced*; D060888:Real-Time Polymerase Chain Reaction; D012128:Respiratory Distress Syndrome / Q000209:etiology*
D008070:Lipopolysaccharides; D003314:Corn Oil