早产绵羊胎儿反复脐带闭塞时下丘脑-垂体-肾上腺轴的激活。

Activation of the hypothalamic-pituitary-adrenal axis with repetitive umbilical cord occlusion in the preterm ovine fetus.

作者信息

Green L R, Kawagoe Y, Fraser M, Challis J R, Richardson B S

机构信息

Department of Obstetrics and Gynecology, London, Ontario, Canada.

出版信息

J Soc Gynecol Investig. 2000 Jul-Aug;7(4):224-32.

PMID:10964021

Abstract

OBJECTIVE

To determine whether repeated hypoxic insults with umbilical cord occlusion over 4 days will lead to activation of the hypothalamic-pituitary-adrenal (HPA) axis altered adrenocortical responsiveness in the preterm ovine fetus.

METHODS

Umbilical cord occlusions of 90 seconds duration were performed every 30 minutes for 3 to 5 hours each day (experimental group n = 7, control group n = 7; at 112-116 days' gestation, term = 147 days). Arterial blood was sampled at predetermined times for blood gases and pH, plasma ACTH, and cortisol. Pituitary proopiomelanocortin (POMC) and glucocorticoid receptor (GR) mRNA also were localized and quantified by in situ hybridization.

RESULTS

During umbilical cord occlusions fetal arterial oxygen pressure (approximately 17 mmHg) and pH (approximately 0.05) decreased, and carbon dioxide pressure increased (approximately 8 mmHg) as measured on days 1 and 4, but with no cumulative blood gas or pH change over successive occlusions for any of the 4 study days. Plasma ACTH increased, as measured after cord occlusion and over the course of successive cord occlusions on days 1 and 4, and returned to control values by the next day. The cumulative increase in ACTH was much less on day 4 than day 1 (15 +/- 3 compared with 101 +/- 25 pg/mL, P <.05). Plasma cortisol increased, as measured after cord occlusion and over the course of successive cord occlusions on day 4 only (2.7 +/- 0.4 to 4. 7 +/- 0.3 ng/mL, P <.05). POMC mRNA increased 2.5-fold in the pars distalis of the pituitaries from cord occlusion compared to control fetuses, but was unchanged in the pars intermedia. GR mRNA, which was detected in the pars distalis only, was unaltered.

CONCLUSION

Repetitive umbilical cord occlusion in the preterm ovine fetus resulted in the activation of the HPA axis, with increased adrenocortical responsiveness over time, and involved differential regulation of POMC mRNA expression in the pars distalis and pars intermedia of the pituitary, but with no change in GR.

摘要

目的

确定在4天内通过脐带闭塞进行反复低氧刺激是否会导致早产绵羊胎儿下丘脑 - 垂体 - 肾上腺（HPA）轴激活并改变肾上腺皮质反应性。

方法

每天每隔30分钟进行一次持续90秒的脐带闭塞，每次持续3至5小时（实验组n = 7，对照组n = 7；妊娠112 - 116天，足月为147天）。在预定时间采集动脉血检测血气、pH值、血浆促肾上腺皮质激素（ACTH）和皮质醇。垂体阿黑皮素原（POMC）和糖皮质激素受体（GR）mRNA也通过原位杂交进行定位和定量。

结果

在脐带闭塞期间，第1天和第4天测量发现胎儿动脉血氧分压（约17 mmHg）和pH值（约0.05）下降，二氧化碳分压升高（约8 mmHg），但在4个研究日中的任何一天，连续闭塞期间血气或pH值均无累积变化。脐带闭塞后及第1天和第4天连续脐带闭塞过程中测量发现血浆ACTH升高，第二天恢复到对照值。第4天ACTH的累积增加量比第1天少得多（15±3与101±25 pg/mL，P <.05）。仅在第4天脐带闭塞后及连续脐带闭塞过程中测量发现血浆皮质醇升高（2.7±0.4至4.7±0.3 ng/mL，P <.05）。与对照胎儿相比，脐带闭塞后垂体远侧部POMC mRNA增加2.5倍，但中间部未改变。GR mRNA仅在远侧部检测到，未发生改变。