Chen Chung-Ming, Wang Leng-Fang, Chou Hsiu-Chu, Lang Yaw-Dong, Lai Yi-Ping
Department of Pediatrics, Taipei Medical University Hospital, Taiwan.
Pediatr Res. 2007 Aug;62(2):128-33. doi: 10.1203/PDR.0b013e3180987202.
Pulmonary oxygen toxicity plays an important role in the lung injury process that leads to the development of bronchopulmonary dysplasia. Connective tissue growth factor (CTGF) is a fibroblast mitogen and promoter of collagen deposition. We investigated the effects of postnatal hyperoxia on lung collagen and CTGF expression in rats. Rat pups were exposed to 7 d of >95% O2 and a further 3 wk of 60% O2. CTGF mRNA and protein expression increased after hyperoxia treatment, and the values were significantly higher in hyperoxia-exposed rats on postnatal d 7 and 14. Lung collagen levels increased as rats aged, and the values were comparable between room air-exposed and hyperoxia-exposed rats on postnatal d 7 and 14 and were significantly higher in hyperoxia-exposed rats on postnatal d 21 and 28. Increases in CTGF mRNA and protein expressions preceded the onset of increased lung collagen. These data demonstrate that CTGF is up-regulated at time points preceding the fibrotic phase of the lung injury adding credence to the hypothesis that CTGF seems to be involved in the pathogenesis of hyperoxia-induced lung fibrosis and an anti-CTGF strategy might attenuate hyperoxia-induced lung fibrosis.
肺氧中毒在导致支气管肺发育不良的肺损伤过程中起重要作用。结缔组织生长因子（CTGF）是一种成纤维细胞有丝分裂原和胶原蛋白沉积的促进剂。我们研究了出生后高氧对大鼠肺胶原蛋白和CTGF表达的影响。将新生大鼠暴露于>95%氧气环境7天，然后再暴露于60%氧气环境3周。高氧处理后CTGF mRNA和蛋白表达增加，在出生后第7天和第14天，暴露于高氧环境的大鼠中这些值显著更高。随着大鼠年龄增长，肺胶原蛋白水平升高，在出生后第7天和第14天，暴露于室内空气和高氧环境的大鼠之间的值相当，而在出生后第21天和第28天，暴露于高氧环境的大鼠中该值显著更高。CTGF mRNA和蛋白表达的增加先于肺胶原蛋白增加的开始。这些数据表明，在肺损伤纤维化阶段之前的时间点CTGF被上调，这支持了CTGF似乎参与高氧诱导的肺纤维化发病机制的假说，并且抗CTGF策略可能减轻高氧诱导的肺纤维化。
