Kelly F J, Lubec G
Rayne Institute, St. Thomas' Hospital, London, England.
Pediatr Res. 1995 Sep;38(3):286-91. doi: 10.1203/00006450-199509000-00003.
Support of preterm infants with ventilation and oxygen therapy frequently leads to the development of chronic lung disease. Oxidative stress, through the generation of excess oxygen free radicals, is thought to play a major role in this condition. At present the radical species responsible for oxidative lung injury is not known, and effective antioxidant based therapies are not available. The purpose of this study was to determine whether hydroxyl radicals, potent reactive oxygen species, are involved in chronic oxidative lung injury. To obtain this information we developed a animal model of chronic lung injury using the preterm guinea pig and analyzed lung tissue from these pups for o-tyrosine, a specific marker of hydroxyl radical attack. In normoxia control pups the pulmonary content of o-tyrosine was low during the first 4 wk of life (range 0.11-0.12% tyrosine). Pups maintained in 85% oxygen were found to have increasing lung o-tyrosine over this period (d 7, 0.51%; d 14, 0.8%; d 21, 1.28%; d 28, 1.45% tyrosine). From d 21, the nonenzymatic glycosylation end product, N-epsilon-carboxymethyllysine was also present in significantly increased amounts in hyperoxic-exposed pups. These results implicate hydroxyl radicals as a significant oxidizing species in hyperoxic lung injury and provide a basis for understanding collagen deposition in the neonatal lung.
对早产儿进行通气和氧疗常常会导致慢性肺病的发展。氧化应激通过产生过量的氧自由基，被认为在这种病症中起主要作用。目前，尚不清楚导致肺氧化损伤的自由基种类，也没有有效的基于抗氧化剂的治疗方法。本研究的目的是确定羟基自由基（一种强活性氧物质）是否参与慢性氧化性肺损伤。为了获得这一信息，我们使用早产豚鼠建立了慢性肺损伤动物模型，并分析了这些幼崽肺组织中的邻酪氨酸（羟基自由基攻击的一种特异性标志物）。在常氧对照组幼崽中，出生后前4周肺组织中邻酪氨酸的含量较低（占酪氨酸的0.11% - 0.12%）。在此期间，处于85%氧气环境中的幼崽肺组织中邻酪氨酸含量不断增加（第7天，0.51%；第14天，0.8%；第21天，1.28%；第28天，1.45%酪氨酸）。从第21天起，在高氧暴露幼崽中，非酶糖基化终产物N - ε - 羧甲基赖氨酸的含量也显著增加。这些结果表明羟基自由基是高氧肺损伤中的一种重要氧化物质，并为理解新生儿肺中胶原蛋白沉积提供了依据。
