Neonatal Hyperoxia Contributes Additively to Cigarette Smoke-Induced Chronic Obstructive Pulmonary Disease Changes in Adult Mice

作者：McGrath Morrow Sharon A^*; Lauer Thomas; Collaco J Michael; Yee Min; O'Reilly Michael; Mitzner Wayne; Neptune Enid; Wise Robert; Biswal Shyam

来源：American Journal of Respiratory Cell and Molecular Biology, 2011, 45(3): 610-616.

DOI：10.1165/rcmb.2010-0259OC

• early postnatal hyperoxia
• airspace abnormalities
• chronic cigarette smoke exposure
• chronic obstructive pulmonary disease

The extent by which early postnatal lung injury contributes to the development of chronic obstructive pulmonary disease (COPD) in the adult is unclear. We hypothesized that exposure to hyperoxia during early postnatal life can augment lung changes caused by adult chronic cigarette smoke(CS) exposure. C57BL/6J mice (1 d old) were exposed to hyperoxia (O-2) for 5 days. At 1 month of age, half of the O-2-exposed mice and half of the control mice were placed in a CS chamber for 6 months. After exposure to CS, mice underwent quasistatic pressure-volume curve and mean chord length measurements; quantification of pro-Sp-c expression; and measurement of lung IL-8/KC, CXCR2/IL8R alpha, TNF-alpha, and IL-6 mRNA by real-time PCR. Adult mice exposed to O-2+CS had significantly larger chord length measurements (P < 0.02) and lung volumes at 35 cm H2O (P < 0.05) compared with all other groups. They also had significantly less pro-Sp-c protein and surfactant protein C mRNA expression (P < 0.003). Mice exposed to O-2+CS and CS-only mice had significantly higher lung resistance and longer mean time constants (P < 0.01), significantly more inflammatory cells in the bronchoalveolar lavage fluid (P < 0.03), and significantly higher levels of lung CXCR2/IL8R alpha mRNA compared with mice not exposed to smoke (P, 0.02). We conclude that exposure to early postnatal hyperoxia contributed additively to CS-induced COPD changes in adult mice. These results may be relevant to a growing population of preterm children who sustained lung injury in the newborn period and may be exposed to CS in later life.

• 出版日期2011-9