Carmichael L, Sadowsky D, Olson D, Challis J, Richardson B
Department of Obstetrics and Gynaecology, Lawson Research Institute, University of Western Ontario, London, Canada.
J Soc Gynecol Investig. 1997 Jan-Feb;4(1):8-14. doi: 10.1016/S1071-5576(96)00039-1.
The purpose of this study was to determine whether activation of the hypothalamic-pituitary-adrenal (HPA) axis and uteroplacental prostaglandin (PG) response occur before metabolic deterioration with a progressive decrease in fetal oxygenation.
Twenty-one chronically catheterized fetal sheep were studied between 126 and 135 days' gestation during a 24-hour normoxic control period and subsequently during 4 experimental days of either prolonged and graded hypoxemia, induced by progressively lowering the maternal inspired oxygen concentration (induced hypoxia, n = 12), or continued study on room air (control, n = 6; spontaneous hypoxia, n = 3). Fetal arterial blood was sampled daily for blood gases and pH, immunoreactive ACTH, cortisol, and PGE2. Placental cotyledons were obtained at the end of the experiment for measurement of prostaglandin-H synthase (PGHS) enzymatic activity.
For all hypoxia group measurements, progressive reduction in fetal oxygenation resulted in little change in either plasma ACTH or cortisol until arterial O2 saturation was close to 30% with metabolic acidosis onsetting. This was in keeping with activation of the HPA axis at this time, because ACTH and cortisol values showed a strong linear correlation (r = 0.77, P < .01). Fetal plasma PGE2 concentrations and cotyledonary PGHS enzymatic activity, although somewhat higher in the hypoxia group animals, were not changed significantly.
In response to prolonged and graded hypoxemia in the ovine fetus, activation of the HPA axis occurs only when the degree of hypoxemia is pronounced and close to that associated with metabolic deterioration, which may limit the time for any uteroplacental response and the ability to initiate labor.
本研究旨在确定下丘脑 - 垂体 - 肾上腺（HPA）轴的激活和子宫胎盘前列腺素（PG）反应是否在胎儿氧合逐渐降低导致代谢恶化之前发生。
对21只慢性插管的胎羊在妊娠126至135天期间进行研究，先进行24小时的常氧对照期，随后在4个实验日中，通过逐步降低母体吸入氧浓度诱导进行长时间分级低氧血症（诱导性低氧，n = 12），或在室内空气中继续研究（对照，n = 6；自发性低氧，n = 3）。每天采集胎儿动脉血用于检测血气、pH、免疫反应性促肾上腺皮质激素（ACTH）、皮质醇和前列腺素E2（PGE2）。实验结束时获取胎盘子叶用于测量前列腺素 - H合成酶（PGHS）的酶活性。
对于所有低氧组测量，胎儿氧合逐渐降低导致血浆ACTH或皮质醇几乎没有变化，直到动脉血氧饱和度接近30%且代谢性酸中毒开始。这与此时HPA轴的激活一致，因为ACTH和皮质醇值显示出很强的线性相关性（r = 0.77，P <.01）。胎儿血浆PGE2浓度和子叶PGHS酶活性，虽然在低氧组动物中略高，但没有显著变化。
对于绵羊胎儿长时间分级低氧血症，HPA轴仅在低氧程度明显且接近与代谢恶化相关的程度时才会激活，这可能会限制子宫胎盘反应的时间和发动分娩的能力。
