期刊
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
卷 300, 期 3, 页码 L362-L369出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.00278.2010
关键词
pulmonary edema; apoptosis; necrosis; nitric oxide; airway injury
资金
- National Institutes of Health [5U54 ES-017218, 5U01 ES-015676, GM-42056]
Yadav AK, Doran SF, Samal AA, Sharma R, Vedagiri K, Postlethwait EM, Squadrito GL, Fanucchi MV, Roberts LJ 2nd, Patel RP, Matalon S. Mitigation of chlorine gas lung injury in rats by postexposure administration of sodium nitrite. Am J Physiol Lung Cell Mol Physiol 300: L362-L369, 2011. First published December 10, 2010; doi:10.1152/ajplung.00278.2010.-Nitrite (NO2-) has been shown to limit injury to the heart, liver, and kidneys in various models of ischemia-reperfusion injury. Potential protective effects of systemic NO2- in limiting lung injury or enhancing repair have not been documented. We assessed the efficacy and mechanisms by which postexposure intraperitoneal injections of NO2- mitigate chlorine (Cl-2)-induced lung injury in rats. Rats were exposed to Cl-2 (400 ppm) for 30 min and returned to room air. NO2- (1 mg/kg) or saline was administered intraperitoneally at 10 min and 2, 4, and 6 h after exposure. Rats were killed at 6 or 24 h. Injury to airway and alveolar epithelia was assessed by quantitative morphology, protein concentrations, number of cells in bronchoalveolar lavage (BAL), and wet-to-dry lung weight ratio. Lipid peroxidation was assessed by measurement of lung F-2-isoprostanes. Rats developed severe, but transient, hypoxemia. A significant increase of protein concentration, neutrophil numbers, airway epithelia in the BAL, and lung wet-to-dry weight ratio was evident at 6 h after Cl-2 exposure. Quantitative morphology revealed extensive lung injury in the upper airways. Airway epithelial cells stained positive for terminal deoxynucleotidyl-mediated dUTP nick end labeling (TUNEL), but not caspase-3. Administration of NO2- resulted in lower BAL protein levels, significant reduction in the intensity of the TUNEL-positive cells, and normal lung wet-to-dry weight ratios. F-2-isoprostane levels increased at 6 and 24 h after Cl-2 exposure in NO2- - and saline-injected rats. This is the first demonstration that systemic NO2- administration mitigates airway and epithelial injury.
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