Bhandari V, Johnson L, Smith-Kirwin S, Vigliotta G, Funanage V, Chander A
Department of Pediatrics, Albert Einstein Medical Center, 5501 Old York Road, Philadelphia, PA 19141, USA.
Lung. 2002;180(6):301-17. doi: 10.1007/s00408-002-0102-y.
Nitric oxide (NO) alone or in conjunction with hyperoxia can have protective or detrimental effects on the lung. Our hypothesis was that hyperoxia in conjunction with NO would result in increased cellular dysfunction and apoptotic cell death in adult and fetal Type II pneumocytes (TIIP) in a dose-dependent manner. The TIIP were obtained from adult and 19-day fetal rat lungs. The TIIP were then exposed to 100, 200 and 500 micro M of the NO-donor, Glyco-SNAP-2, alone or in conjunction with 95% oxygen for 24 h. While low-dose NO exposure alone did not increase cytotoxicity, in conjunction with hyperoxia, there was a significant dose-dependent increase in apoptotic cell death of adult TIIP as well as fetal TIIP. Choline incorporation into disaturated phosphatidylcholine was markedly decreased in adult TIIP while the fetal TIIP had similar values as controls. However, the mRNAs of surfactant proteins A, B and C as well as iNOS were significantly reduced in fetal TIIP. Exogenous peroxynitrite also increased nitrotyrosine formation in fetal TIIP as did hyperoxia and NO. The effect of hyperoxia and NO could be abrogated with catalase and superoxide dismutase. These findings may have significant clinical implications in the use of NO in premature infants.
一氧化氮（NO）单独或与高氧联合使用时，对肺脏可能产生保护作用或有害影响。我们的假设是，高氧与NO联合使用会以剂量依赖的方式导致成年和胎儿II型肺上皮细胞（TIIP）的细胞功能障碍增加和凋亡性细胞死亡。TIIP取自成年大鼠和19天胎龄的大鼠肺脏。然后将TIIP单独或与95%氧气联合暴露于100、200和500微摩尔的NO供体Glyco-SNAP-2中24小时。虽然单独低剂量NO暴露不会增加细胞毒性，但与高氧联合使用时，成年TIIP和胎儿TIIP的凋亡性细胞死亡均有显著的剂量依赖性增加。成年TIIP中胆碱掺入二饱和磷脂酰胆碱的量明显减少，而胎儿TIIP的值与对照组相似。然而，胎儿TIIP中表面活性蛋白A、B和C以及诱导型一氧化氮合酶的mRNA显著减少。外源性过氧亚硝酸盐以及高氧和NO也会增加胎儿TIIP中的硝基酪氨酸形成。过氧化氢酶和超氧化物歧化酶可以消除高氧和NO的作用。这些发现可能对早产儿使用NO具有重要的临床意义。
