Sinha Anuj, Muthiah Kathirvel, Jiang Weiwu, Couroucli Xanthi, Barrios Roberto, Moorthy Bhagavatula
Section of Neonatology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
Toxicol Sci. 2005 Sep;87(1):204-12. doi: 10.1093/toxsci/kfi226. Epub 2005 Jun 15.
Supplemental oxygen, frequently used in premature infants, has been implicated in the development of bronchopulmonary dysplasia (BPD). While the mechanisms of oxygen-induced lung injury are not known, reactive oxygen species (ROS) are most likely involved in the process. Here, we tested the hypothesis that upregulation of cytochrome P450 (CYP) 1A isoforms in lung and liver may lead to protection against hyperoxic lung injury. Adult male Sprague-Dawley rats were pretreated with the CYP1A inducer beta-naphthoflavone (beta-NF) (80 mg/kg/day), once daily for 4 days, followed by exposure to hyperoxic environment (O2 > 95%) or room air (normoxia) for 60 h. Pleural effusions were measured as estimates of lung injury. Activities of hepatic and pulmonary CYP1A1 were determined by measurement of ethoxyresorufin O-deethylation (EROD) activity. Northern hybridization and Western blot analysis of lung and liver were performed to assess mRNA and protein levels, respectively. Our results showed that beta-NF-treated animals, which displayed the highest pulmonary and hepatic induction in EROD activity (10-fold and 8-fold increase over corn oil (CO) controls, respectively), offered the most protective effect against hyperoxic lung injury, p < 0.05. Northern and Western blot analysis correlated well with enzyme activities. Our results showed an inverse correlation between pulmonary and hepatic CYP1A expression and the extent of lung injury, which supports the hypothesis that CYP1A enzyme plays a protective role against oxygen-mediated tissue damage.
常用于早产儿的补充氧气与支气管肺发育不良（BPD）的发生有关。虽然氧诱导肺损伤的机制尚不清楚，但活性氧（ROS）很可能参与了这一过程。在此，我们检验了一个假设，即肺和肝脏中细胞色素P450（CYP）1A亚型的上调可能导致对高氧肺损伤的保护作用。成年雄性Sprague-Dawley大鼠用CYP1A诱导剂β-萘黄酮（β-NF）（80毫克/千克/天）预处理，每天一次，共4天，然后暴露于高氧环境（氧气>95%）或室内空气（常氧）60小时。测量胸腔积液作为肺损伤的估计指标。通过测量乙氧异羟肟酸O-脱乙基酶（EROD）活性来测定肝脏和肺中CYP1A1的活性。分别对肺和肝脏进行Northern杂交和Western印迹分析，以评估mRNA和蛋白质水平。我们的结果表明，β-NF处理的动物在EROD活性方面表现出最高的肺和肝脏诱导（分别比玉米油（CO）对照组增加10倍和8倍），对高氧肺损伤提供了最大的保护作用，p<0.05。Northern和Western印迹分析与酶活性相关性良好。我们的结果表明，肺和肝脏中CYP1A的表达与肺损伤程度呈负相关，这支持了CYP1A酶对氧介导的组织损伤起保护作用的假设。
