Takizawa T, Ikeda Y, Kawahata M, Togashi H, Yamamoto M, Arishima K, Masaoka T
Department of Developmental and Reproductive Biotechnology, Azabu University School of Veterinary Medicine, Kanagawa, Japan.
J Vet Med Sci. 1998 Mar;60(3):377-9. doi: 10.1292/jvms.60.377.
This work was conducted to determine whether aspirin and ibuprofen, when administered prenatally may potentiate a reopening of the neonatal ductus arteriosus (DA) induced by PGE2 after postnatal closure. In the first experiment, a subcutaneous injection of PGE2 (4 microgram(s)) was administered to newborn rats 3 hr after a Cesarean delivery from pregnant females which had been orally given 100 or 300 mg/kg/day of aspirin and 10 or 30 mg/kg/day of ibuprofen on days 18, 19 and 20 of gestation. The ratio of the DA to the pulmonary artery (PA) was determined at intervals after the injection. The DA/PA ratio was significantly higher in newborn rats from mothers who were transplacentally administered these agents than the control. We also examined the hypothesis that maternal treatment with nonsteroidal anti-inflammatory drugs (NSAID), such as aspirin and ibuprofen, inhibits the catabolism of PGE2 and that the increased reopening of the DA was partly due to this inhibition. 15-hydroxy prostaglandin dehydrogenase (15-PGDH) in neonatal lungs, the key enzyme involved in catalyzing PGE2 to convert it to its inactive metabolite 15-keto-PGE2, was not affected by maternal treatment with aspirin and ibuprofen. These results suggest that the increased ductal responsiveness to PGE2 in newborn rats was a common response after maternal NSAID treatment, but the catabolism of PGE2 in the lungs did not always contribute to this response.
本研究旨在确定产前给予阿司匹林和布洛芬是否会增强产后关闭的新生儿动脉导管（DA）在出生后因前列腺素E2（PGE2）诱导的重新开放。在第一个实验中，对妊娠第18、19和20天口服给予100或300 mg/kg/天阿司匹林及10或30 mg/kg/天布洛芬的孕鼠进行剖宫产，在新生大鼠出生后3小时皮下注射PGE2（4微克）。注射后每隔一段时间测定DA与肺动脉（PA）的比值。经胎盘给予这些药物的母鼠所生新生大鼠的DA/PA比值显著高于对照组。我们还检验了这样一种假设，即母体使用非甾体抗炎药（NSAID）如阿司匹林和布洛芬进行治疗会抑制PGE2的分解代谢，而DA重新开放增加部分归因于这种抑制作用。新生儿肺中的15-羟基前列腺素脱氢酶（15-PGDH）是催化PGE2转化为无活性代谢物15-酮基-PGE2的关键酶，其不受母体阿司匹林和布洛芬治疗的影响。这些结果表明，母体NSAID治疗后新生大鼠导管对PGE2反应性增加是一种常见反应，但肺中PGE2的分解代谢并不总是导致这种反应。
