Apoptosis in neonatal murine lung exposed to hyperoxia
Apoptosis in neonatal murine lung exposed to hyperoxia
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DOI：
10.1165/ajrcmb.25.2.4362
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发表时间：
2001-08-01
影响因子：
6.4
通讯作者：
Stahl, J
中科院分区：
文献类型：
--
作者：
McGrath-Morrow, SA;Stahl, J
新生儿期暴露于高浓度氧气可能损害肺生长，是支气管肺发育不良的一个主要因素。高氧损伤引起的细胞死亡可能通过凋亡或非凋亡途径发生，我们对确定暴露于高氧的新生小鼠肺中发生的细胞死亡类型感兴趣。我们发现，在92%高氧环境下出生和长大的新生小鼠的肺部中，Bax信使RNA（一种与细胞凋亡相关的基因）水平升高。接下来，我们使用末端脱氧核糖核苷转移酶介导的脱氧尿苷三磷酸生物素镍端标记法，在3.5、4.5和5.5 d大的新生儿肺中测定了暴露于高氧条件下的新生小鼠肺中发生的细胞凋亡程度。3.5、4.5、5.5 d龄小鼠肺外周凋亡细胞数量明显高于室温对照组。此外，随着暴露时间的延长，肺中凋亡细胞的数量增加。暴露于高氧条件下的小鼠肺支气管细胞，在暴露于氧48小时后发生生长停滞。利用膜联蛋白V结合，发现这些细胞在高氧暴露72小时后，坏死细胞死亡是细胞死亡的主要形式。我们得出结论，92%的高氧对暴露于高氧环境下的新生小鼠造成显著的肺损伤，并且肺中凋亡细胞的数量随着暴露时间的延长而增加。在肺发育的关键时期，高氧暴露导致的细胞凋亡增加可能是暴露于高氧浓度的动物肺生长和重塑受损的一个重要因素。最后，新生儿肺高氧损伤细胞似乎同时发生凋亡和非凋亡细胞死亡。
Exposure to high concentrations of oxygen in the neonatal period may impair lung growth and is a major contributing factor to the development of bronchopulmonary dysplasia. Cell death from hyperoxic injury may occur through either an apoptotic or nonapoptotic pathway, and we were interested in determining the type of cell death that occurs in the lung of neonatal mice exposed to hyperoxia. We found increased levels of Bax messenger RNA, a gene associated with apoptosis, in the lungs of neonatal mice born and raised in 92% hyperoxia. We next determined the extent of apoptosis taking place in the lungs of neonatal mice exposed to hyperoxia using terminal deoxyribonucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling in 3.5-, 4.5-, and 5.5-d-old neonatal lung. The number of apoptotic cells in peripheral lung was significantly higher in the 3.5-, 4.5-, and 5.5-d-old mice treated with oxygen compared with that in the room-air control mice. Further, the number of apoptotic cells in the lung increased with longer exposure duration. In murine lung bronchus cells exposed to hyperoxia, growth arrest occurred after 48 h of oxygen exposure. Using annexin V binding, necrotic cell death was found to be the major form of cell death in these cells after 72 h of hyperoxic exposure. We conclude that 92% hyperoxia causes significant lung injury in neonatal mice exposed to hyperoxia, and that the number of apoptotic cells in the lung increases the longer the duration of exposure. The increase in apoptosis from hyperoxic exposure during a critical period of lung development may be an important factor in the impaired lung growth and remodeling that occur in animals exposed to high oxygen concentrations. Finally, it appears that hyperoxic injured cells in neonatal lung undergo both apoptotic and nonapoptotic cell death.