Coleman Rebecca J, Beharry Kay D A, Brock Romy S, Abad-Santos Patricia, Abad-Santos Matthew, Modanlou Houchang D
Department of Pediatrics, University of California Irvine, Irvine, California 92868, USA.
Pediatr Res. 2008 Jul;64(1):50-5. doi: 10.1203/PDR.0b013e31817307ac.
Oxygen fluctuation patterns in preterm infants who develop retinopathy of prematurity (ROP) are varied and poorly represented in animal models. We examined the hypothesis that clustered (CL) episodes of hypoxia during hyperoxia results in a more severe form of oxygen-induced retinopathy (OIR) than dispersed episodes. Rat pups were exposed to alternating cycles of 1) 50% O2 with three CL episodes of 12% O2 every 6 h; or 2) 50% O2 with one episode of 12% O2 every 2 h, for 7 (P7) or 14 (P14) days postnatal age. Pups were killed after hyperoxia, or placed in room air (RA) until P21. RA littermates were killed at P7, P14, and P21. Systemic and ocular vascular endothelial growth factor (VEGF), soluble VEGFR-1 (sVEGFR-1), insulin-like growth factor I (IGF-I), and growth hormone were examined. All hyperoxia-exposed retinas had evidence of neovascularization. Animals in the CL group had a more severe form of OIR at P21 evidenced by vascular tufts, leaky vessels, retinal hemorrhage, and vascular overgrowth. These characteristics were associated with low body weight; high systemic and ocular VEGF; and low systemic and high ocular sVEGFR-1 and IGF-I. These data suggest that preterm infants who experience CL fluctuations in Pao2 during supplemental O2 therapy are at a higher risk for severe ROP.
发生早产儿视网膜病变（ROP）的早产儿的氧波动模式各不相同，且在动物模型中表现不佳。我们检验了这样一个假设：与分散发作相比，高氧期间的缺氧聚集（CL）发作会导致更严重的氧诱导性视网膜病变（OIR）。将新生大鼠幼崽暴露于交替循环中：1）50%氧气，每6小时有3次12%氧气的CL发作；或2）50%氧气，每2小时有1次12%氧气的发作，持续至出生后7天（P7）或14天（P14）。高氧暴露后处死幼崽，或将其置于室内空气（RA）中直至P21。RA同窝幼崽在P7、P14和P21处死。检测全身和眼部血管内皮生长因子（VEGF）、可溶性VEGFR-1（sVEGFR-1）、胰岛素样生长因子I（IGF-I）和生长激素。所有高氧暴露的视网膜都有新生血管形成的证据。CL组动物在P21时OIR更严重，表现为血管丛、血管渗漏、视网膜出血和血管过度生长。这些特征与低体重、全身和眼部高VEGF、全身低和眼部高sVEGFR-1及IGF-I有关。这些数据表明，在补充氧气治疗期间经历Pao2的CL波动的早产儿发生严重ROP的风险更高。
