Abstract
Aim:
To investigate the effects of inhaled nitric oxide (NO) on pulmonary inflammation, apoptosis, peroxidation and protein nitration in a rat model of acute lung injury (ALI) induced by meconium.
Methods:
Twenty-four healthy male Sprague-Dawley rats were randomly devided into 3 groups (n=8): meconium-induced ALI with intratracheal instillation of 1 mL/kg saline (Mec/saline group), continuous inhalation of NO at 20 μL/L. (Mec/iNO), and the control group (control). Electromicroscopic examination was used to determine the extent of epithelial apoptosis. TUNEL was used to detect DNA fragmentation in pulmonary apoptotic cells, expressed as the apoptosis index (AI). Western blotting was used to detect pulmonary inducible NO synthase (iNOS) expression. RT-PCR was used to detect interleukin (IL)-1β mRNA expression. Cell count inbronchoalveolar lavage (BAL), myeloperoxidase (MPO) activity, as well as malondialdehyde (MDA) and nitrotyrosine formation, the markers of toxic NO-superoxide pathway in rat lung parenchyma specimens, were also examined.
Results:
Expression of iNOS protein and IL-1β mRNA were increased significantly in the Mec/saline group (both P<0.01) compared with the control group. BAL cell count, MPO activity, lung injury score, pulmonary AI, MDA level and nitrotyrosine formation were also increased significantly (all P<0.01). The meconium-induced iNOS protein and IL-1β mRNA expression were inhibited significantly by NO inhalation when compared with the Mec/saline group (both P<0.01). BAL cell count, MPO activity and lung injury score were also decreased significantly (P<0.01 or P<0.05). However, there were no statistical differences in MDA level, nitrotyrosine formation or pulmonary AI between the Mec/saline and Mec/iNO groups. Electromicroscopic examination revealed a significant degree of epithelial apoptosis in both the Mec/saline and Mec/iNO groups.
Conclusions:
Early continuous inhalation of NO 20 μL/L may protect the lungs from inflammatory injury, but does not decrease epithelial apoptosis or lung nitrotyrosine formation. Inhalation of NO alone is not associated with a detectable increase in oxidant stress.
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Project supported by the National Natural Science Foundation of China (No 30371498), the Commission of Science and Technology of Zhejiang Province (No 2004C33019) and the Bureau of Education of Zhejiang Province (No 20030304), partly supported by E-Institute of Shanghai Municipal Education Commission (Project No E-04010, China)
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Lu, Mp., Du, Lz., Gu, Wz. et al. Nitric oxide inhalation inhibits inducible nitric oxide synthase but not nitrotyrosine formation and cell apoptosis in rat lungs with meconium-induced injury. Acta Pharmacol Sin 26, 1123–1129 (2005). https://doi.org/10.1111/j.1745-7254.2005.00153.x
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DOI: https://doi.org/10.1111/j.1745-7254.2005.00153.x
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