Kiliç Ilknur, Güven Cengiz, Kilinç Kamer
Department of Pediatrics, Pamukkale University Faculty of Medicine, Denizli, Turkey.
Pediatr Int. 2003 Aug;45(4):375-8. doi: 10.1046/j.1442-200x.2003.01740.x.
Nitric oxide (NO) inhibition with NG-nitro-l-arginine methyl ester (l-NAME) in the last trimester of pregnancy caused intrauterine growth retardation and hind-limb disruptions in rats. In the present study, the effect of maternal NO inhibition with NG-nitro-l-arginine (l-NNA) on hypoxic newborn rats was investigated.
Timed-pregnant rats were obtained on gestational day 17. Four groups of rats were used: control, hypoxic, l-NNA and l-NNA + hypoxic groups. In the last two groups, l-NNA (2 mg/kg bolus, i.p.) was administered to the mothers of pups antenatally on 3 consecutive days. Hypoxia was induced in newborn rats by breathing of a mixture of 8% oxygen and 92% nitrogen for 3 h. Pups were then allowed to inhale normal atmospheric air for 30 min. All newborn rats were decapitated on the first day of life after hypoxia and reoxygenation. Brain, heart, lung, liver, kidney and intestinal tissues were studied biochemically. Hypoxia-induced biochemical changes were determined by measuring lipid peroxidation. Histopathologic examination of lung tissue was performed.
Nitric oxide synthase inhibition in pregnancy did not cause fetal growth retardation. Hypoxia increased lipid peroxidation in all tissues except the heart; this increase was decreased by maternal l-NNA administration in brain, lung, liver and kidney tissues. However, lipid peroxidation was increased by NO synthase inhibition in the intestines. In the lungs, pulmonary hemorrhage was observed in the hypoxic group. Minimal pulmonary hemorrhage was detected in the l-NNA and l-NNA + hypoxic groups.
These data suggest that antenatal administration of an NO synthase inhibitor acts as both a destructive and protective agent in hypoxic newborn rats.
在妊娠晚期用NG-硝基-L-精氨酸甲酯（L-NAME）抑制一氧化氮（NO）会导致大鼠宫内生长迟缓及后肢发育异常。在本研究中，探讨了母体用NG-硝基-L-精氨酸（L-NNA）抑制NO对缺氧新生大鼠的影响。
在妊娠第17天获得定时受孕大鼠。使用四组大鼠：对照组、缺氧组、L-NNA组和L-NNA+缺氧组。在最后两组中，连续3天给幼崽的母亲腹腔注射L-NNA（2mg/kg推注剂量）。通过让新生大鼠吸入8%氧气和92%氮气的混合气体3小时诱导缺氧。然后让幼崽吸入正常大气空气30分钟。所有新生大鼠在缺氧和复氧后的第一天断头。对脑、心、肺、肝、肾和肠组织进行生化研究。通过测量脂质过氧化来确定缺氧诱导的生化变化。对肺组织进行组织病理学检查。
孕期抑制一氧化氮合酶未导致胎儿生长迟缓。缺氧增加了除心脏外所有组织中的脂质过氧化；在脑、肺、肝和肾组织中，母体给予L-NNA可降低这种增加。然而，在肠道中，抑制一氧化氮合酶会增加脂质过氧化。在肺脏方面，缺氧组观察到肺出血。在L-NNA组和L-NNA+缺氧组中检测到轻微肺出血。
这些数据表明，产前给予一氧化氮合酶抑制剂在缺氧新生大鼠中既是一种破坏剂又是一种保护剂。
