Carlos R Q, Seidler F J, Lappi S E, Slotkin T A
Department of Pediatrics, Duke University Medical Center, Durham, N.C.
Biol Neonate. 1991;59(2):69-77. doi: 10.1159/000243325.
Although glucocorticoids are widely used to stimulate fetal/neonatal lung function, they also interfere with cellular development in the central nervous system. Dexamethasone was administered to pregnant rats in late gestation at a dose (0.8 mg/kg) that lies just above the threshold for stimulation of lung surfactant synthesis, and the impact on ornithine decarboxylase (ODC) was evaluated in three brain regions. Dexamethasone treatment produced an initial inhibition of basal ODC activity followed by postnatal elevations, a pattern known to be associated with delays in cell replication and differentiation. Dexamethasone also interfered with the ability of the 1-day-old neonate to turn off ODC acutely in response to a 2-h period of maternal separation; as this response conserves energy in the absence of the dam, the effect of dexamethasone is maladaptive. Additionally, dexamethasone sensitized the neonatal brain to hypoxia: the acute increase of ODC associated with a 2-h exposure to 7% O2 was exacerbated in 8-day-old rats exposed to dexamethasone prenatally. These results suggest that administration of dexamethasone, in doses that promote respiratory competence, delays cell development in the central nervous system and renders the brain more vulnerable to adverse neonatal conditions, such as maternal separation or hypoxia.
尽管糖皮质激素被广泛用于刺激胎儿/新生儿的肺功能，但它们也会干扰中枢神经系统的细胞发育。地塞米松以刚好高于刺激肺表面活性物质合成阈值的剂量（0.8毫克/千克）在妊娠晚期给予怀孕大鼠，并在三个脑区评估其对鸟氨酸脱羧酶（ODC）的影响。地塞米松治疗导致基础ODC活性最初受到抑制，随后在出生后升高，这种模式已知与细胞复制和分化延迟有关。地塞米松还干扰了1日龄新生儿在与母亲分离2小时后急性关闭ODC的能力；由于这种反应在没有母鼠的情况下节省能量，地塞米松的作用是适应不良的。此外，地塞米松使新生儿脑对缺氧敏感：在产前暴露于地塞米松的8日龄大鼠中，与暴露于7%氧气2小时相关的ODC急性增加加剧。这些结果表明，以促进呼吸能力的剂量给予地塞米松会延迟中枢神经系统的细胞发育，并使大脑更容易受到不利新生儿状况的影响，如母亲分离或缺氧。
