Abstract |
Mechanical ventilation can cause structural and functional disturbances in the lung termed ventilator-induced lung injury (VILI). The aim of this study was to evaluate whether BML-111, a lipoxin receptor agonist, could attenuate VILI. Following induction of anesthesia and tracheostomy, Sprague-Dawley rats were ventilated with low tidal volume (6 mL/kg) or high tidal volume (20 mL/kg, HVT) for 4 h. Some rats subjected to HVT ventilation received BML-111 or vehicle (saline) by intraperitoneal injection. Some rats subjected to HVT and BML-111(1 mg/kg) received BOC-2 (a FPR2/ALX antagonist) intraperitoneally 30 min before BML-111. Sham rats were tracheotomized without ventilation. Treatment with BML-111 attenuated VILI, as evidenced by improved oxygenation and reduced histological injury compared with HVT-induced lung injury. BML-111 decreased indices of inflammation such as interleukin 1β, interleukin 6, tumor necrosis factor α, and bronchoalveolar lavage neutrophil infiltration. Administration with BML-111 suppressed the decrement of the nuclear factor κB (NF-κB) inhibitor IκB-α, diminished NF-κB activation, and reduced activation of mitogen-activated protein kinase in VILI. This study indicates that BML-111 attenuated VILI via a NF-κB and mitogen-activated protein kinase dependent mechanism. BML-111 may be a promising strategy for alleviation of VILI in patients subjected to mechanical ventilation.
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Authors | Hongbin Li, Zhouyang Wu, Dan Feng, Jie Gong, Chengye Yao, Yaxin Wang, Shiying Yuan, Shanglong Yao, You Shang |
Journal | Shock (Augusta, Ga.)
(Shock)
Vol. 41
Issue 4
Pg. 311-6
(Apr 2014)
ISSN: 1540-0514 [Electronic] United States |
PMID | 24365886
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- 5(S),6(R)-7-trihydroxyheptanoic acid, methyl ester
- Anti-Inflammatory Agents, Non-Steroidal
- Cytokines
- Heptanoic Acids
- I-kappa B Proteins
- NF-kappa B
- Nfkbia protein, rat
- Receptors, Lipoxin
- Rela protein, rat
- Transcription Factor AP-1
- Transcription Factor RelA
- NF-KappaB Inhibitor alpha
- Peroxidase
- Mitogen-Activated Protein Kinases
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Topics |
- Animals
- Anti-Inflammatory Agents, Non-Steroidal
(pharmacology, therapeutic use)
- Bronchoalveolar Lavage Fluid
(cytology)
- Cytokines
(biosynthesis)
- Drug Evaluation, Preclinical
(methods)
- Heptanoic Acids
(pharmacology, therapeutic use)
- I-kappa B Proteins
(metabolism)
- Male
- Mitogen-Activated Protein Kinases
(metabolism)
- NF-KappaB Inhibitor alpha
- NF-kappa B
(metabolism)
- Peroxidase
(metabolism)
- Phosphorylation
- Rats
- Rats, Sprague-Dawley
- Receptors, Lipoxin
(agonists)
- Transcription Factor AP-1
(metabolism)
- Transcription Factor RelA
(genetics, metabolism)
- Translocation, Genetic
(drug effects)
- Up-Regulation
(drug effects)
- Ventilator-Induced Lung Injury
(metabolism, pathology, prevention & control)
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