Intraamniotic endotoxin increases lung antioxidant enzyme activity in preterm lambs
Intraamniotic endotoxin increases lung antioxidant enzyme activity in preterm lambs
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DOI：
10.1203/01.pdr.0000055769.19891.c4
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发表时间：
2003-04-01
影响因子：
3.6
通讯作者：
Jobe, AH
中科院分区：
文献类型：
--
作者：
Sosenko, IRS;Jobe, AH
羊膜内毒素引起的促炎刺激改善胎羊肺功能，增加表面活性蛋白mRNA表达和蛋白含量，增加肺泡和肺饱和磷脂酰胆碱池，加速肺形态成熟。诱导肺成熟的机制不涉及胎儿皮质醇的增加。内毒素对另一种肺系统——抗氧化酶（AOE）系统成熟的影响尚未被研究。因此，我们假设羊膜内毒素在与那些促进肺功能和表面活性剂成熟的给药剂量和时间表相似的情况下，会加速胎羊的AOE活性。在一项剂量反应研究中，在妊娠125天的绵羊早产前7天给予羊膜内注射1、4、20或100毫克大肠杆菌055:05内毒素。在一项检查分娩前给药时间间隔的研究中，在早产前1、2、4、7或15天间隔注射20mg内毒素。1-100毫克的内毒素剂量显著增加谷胱甘肽过氧化物酶活性；4-100 mg剂量显著增加过氧化氢酶活性，而20-100 mg剂量显著增加总超氧化物歧化酶活性。内毒素处理后2 d内谷胱甘肽过氧化物酶活性升高，4 d内超氧化物歧化酶活性升高，7 d内过氧化氢酶活性升高。在15 d内，AOE没有持续增加。内毒素增加胎儿肺AOE活性的剂量和间隔与产生肺功能成熟和表面活性剂的剂量和间隔相似。因此，与糖皮质激素无关的促炎刺激机制可以诱导胎儿肺AOE系统的成熟。
Proinflammatory stimulation resulting from intraamniotic endotoxin improves lung function, increases surfactant protein mRNA expression and protein content, increases alveolar and lung saturated phosphatidylcholine pools, and accelerates lung morphometric maturation in fetal sheep. The mechanism for induction of lung maturation does not involve an increase in fetal cortisol. The effect of endotoxin on the maturation of a different lung system, the antioxidant enzyme (AOE) system, has not been examined. Therefore, we hypothesized that intraamniotic endotoxin would produce acceleration of AOE activity in fetal sheep at similar doses and schedule of administration to those producing lung functional and surfactant maturation. In a dose-response study, intraamniotic injections of 1, 4, 20, or 100 mg of Escherichia coli 055:05 endotoxin were administered 7 d before preterm delivery of sheep at 125 d gestation. In a study examining time interval of administration before delivery, 20 mg of endotoxin was injected at either 1-, 2-, 4-, 7-, or 15-d intervals before preterm. delivery at 125 d. Doses of 1-100 mg of endotoxin produced significant increases in glutathione peroxidase activity; doses of 4-100 mg significantly increased catalase activity, whereas doses of 20-100 mg resulted in significant increases in total superoxide dismutase activity. Glutathione peroxidase activity was elevated within 2 d, whereas superoxide dismutase was increased by 4 d and catalase activity increased by 7 d after endotoxin. No AOE increases were sustained for 15 d. Endotoxin increased fetal lung AOE activity at similar dosing amounts and intervals to those producing maturation of lung function and surfactant. Thus, mechanisms involving proinflammatory stimulation, unrelated to glucocorticoid hormones, can induce maturation of the AOE system of the fetal lung.