Thaete Larry G, Neerhof Mark G
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Evanston, IL, USA.
Am J Obstet Gynecol. 2006 May;194(5):1377-83. doi: 10.1016/j.ajog.2005.11.019. Epub 2006 Mar 30.
The objective of the study was to evaluate the role of endothelin-1 and platelet-activating factor in ischemia/reperfusion-induced fetal growth restriction in the rat.
On day 17 of gestation, the right uterine and ovarian arteries were occluded for 30 minutes in experimental but not sham-operated rats. All rats received endothelin receptor A antagonist, A-127722 (10 mg/kg per day), platelet-activating factor antagonist, WEB-2086 (1 mg/kg), or vehicle. On gestational day 21, litter size, fetal viability, and fetal and placental weights were recorded. Reverse transcription-polymerase chain reaction for phospholipase A2-IIA and preproendothelin-1 messenger ribonucleic acid was performed on uterus and placentas from each uterine horn. Groups were compared statistically by analysis of variance.
Ischemia/reperfusion reduced fetal weights, in both the ischemic horn and the nonischemic horn (P < .001). Antagonism of either endothelin receptor A or platelet-activating factor normalized fetal growth in both horns. Neither placental weight nor the incidence of fetal demise was affected by ischemia/reperfusion. Phospholipase A2-IIA and preproendothelin-1 messenger ribonucleic acid expression did not differ between right and left uterine horns in any group. Uterine and placental tissues in the ischemia/reperfusion group exhibited increased phospholipase A2-IIA (P < .01) but not preproendothelin-1.
Endothelin-1 and platelet-activating factor are both important mediators in the pathophysiology of ischemia/reperfusion-induced fetal growth restriction in the rat, contributing to the fetal growth restriction observed in both the ischemic and nonischemic horns. Antagonism of either mediator produces normal fetal growth in this model of fetal growth restriction.
本研究的目的是评估内皮素 -1 和血小板活化因子在大鼠缺血/再灌注诱导的胎儿生长受限中的作用。
在妊娠第17天，对实验大鼠而非假手术大鼠的右子宫和卵巢动脉进行30分钟的闭塞。所有大鼠接受内皮素A受体拮抗剂A - 127722（每天10毫克/千克）、血小板活化因子拮抗剂WEB - 2086（1毫克/千克）或载体。在妊娠第21天，记录产仔数、胎儿存活率以及胎儿和胎盘重量。对每个子宫角的子宫和胎盘进行磷脂酶A2-IIA和前内皮素-1信使核糖核酸的逆转录 - 聚合酶链反应。通过方差分析对各组进行统计学比较。
缺血/再灌注降低了缺血侧子宫角和非缺血侧子宫角的胎儿体重（P <.001）。内皮素A受体或血小板活化因子的拮抗作用使两侧子宫角的胎儿生长恢复正常。缺血/再灌注对胎盘重量和胎儿死亡发生率均无影响。任何组的左右子宫角之间磷脂酶A2-IIA和前内皮素-1信使核糖核酸表达均无差异。缺血/再灌注组的子宫和胎盘组织中磷脂酶A2-IIA表达增加（P <.01），但前内皮素-1未增加。
内皮素-1和血小板活化因子都是大鼠缺血/再灌注诱导的胎儿生长受限病理生理学中的重要介质，导致缺血侧和非缺血侧子宫角出现胎儿生长受限。在这种胎儿生长受限模型中，拮抗任何一种介质均可使胎儿生长正常。
