PREECLAMPSIA - AN IMBALANCE IN PLACENTAL PROSTACYCLIN AND THROMBOXANE PRODUCTION

PREECLAMPSIA - AN IMBALANCE IN PLACENTAL PROSTACYCLIN AND THROMBOXANE PRODUCTION
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DOI:
10.1016/s0002-9378(85)80223-4
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发表时间:
1985-01-01
影响因子:
9.8
通讯作者:
WALSH, SW
WALSH, SW
中科院分区:
医学1区
文献类型:
--
作者:
WALSH, SW

文献摘要

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先兆子痫的特征是血管收缩增加,常常伴随着血小板聚集增加,子宫胎盘血流量减少和早产。由于前列环素拮抗血栓烷的血管收缩、血小板聚集和子宫激活作用,故认为胎盘血栓素生成增加与前列环素减少的假说在子痫前期发生时是一致的。新鲜的人足月胎盘在分娩后立即从11例正常妊娠和10例先兆子痫妊娠(血压。140/90毫米汞柱,尿蛋白和GT;0.3克/24小时)。将组织(350 Mg)置于杜尔贝科‘S改良鹰’S培养液6ml中,37℃无菌孵育48h。在代谢摇床中加入95%的氧气和5%的二氧化碳。分别于8、20、32、48h采集标本,用放射免疫法测定其稳定代谢产物血栓素B2,用放射免疫法测定其稳定代谢产物6-酮前列腺素F1α的前列环素。与正常胎盘组织相比,先兆子痫患者胎盘组织中血栓烷的产生显著增加(22.9.+-。4.7比6.3+-。每小时1.5pg/mg,平均+-。Se,P<0.01),而前列环素的产生显著减少(3.0±-)。0.3比6.7。+-。0.5pg/mg/h,P<0.001)。无论是正常胎盘还是子痫前期胎盘,血栓素和前列环素的产生均被吲哚美辛(5µm o l/L)抑制,而花生四烯酸(100 m o l/L)对其无影响(P>0.50)。因此,在正常妊娠期间,胎盘会产生等量的血栓素和前列环素,从而使它们在血管紧张性、血小板聚集和子宫活动方面的生物作用得到平衡。然而,在先兆子痫妊娠中,胎盘产生的血栓素是前列环素的7倍。
Preeclampsia is characterized by increased vasoconstriction frequently associated with increased platelet aggregation, reduced uteroplacental blood flow and premature delivery. Because prostacyclin antagonizes the vasoconstrictor, platelet-aggregating and uterine-activating actions of thromboxane, the hypothesis that placental production of thromboxane was increased coincident with decreased production of prostacyclin was considered in preeclampsia. Fresh human term placentas were obtained immediately after delivery from 11 normal and 10 preeclamptic pregnancies (blood pressure .gtoreq. 140/90 mm Hg, urinary protein > 0.3 gm/24 h). Tissues (350 mg) were incubated sterilely in 6 ml of Dulbecco''s Modified Eagle''s Medium for 48 h at 37.degree. C with 95% oxygen and 5% carbon dioxide in a metabolic shaker. Samples were collected at 8, 20, 32 and 48 h and analyzed for thromboxane by radioimmunoassay of its stable metabolite, thromboxane B2 and for prostacyclin by radioimmunoassay of its stable metabolite, 6-ketoprostaglandin F1.alpha.. The production of thromboxane was significantly increased in preeclamptic vs. normal placental tissue (22.9 .+-. 4.7 vs. 6.3 .+-. 1.5 pg/mg per h, mean .+-. SE, P < 0.01), whereas the production of prostacyclin was significantly decreased (3.0 .+-. 0.3 vs. 6.7 .+-. 0.5 pg/mg per h, P < 0.001). In both normal and preeclamptic placentas, the production rates of thromboxane and prostacyclin were inhibited by indomethacin (5 .mu.mol/l) and not affected (P > 0.50) by arachidonic acid (100 .mu.mol/l). Therefore, during normal pregnancy, the placenta produces equivalent amounts of thromboxane and prostacyclin, so that their biologic actions on vascular tone, platelet aggregation and uterine activity will be balanced. In preeclamptic pregnancy, however, the placenta produces 7 times more thromboxane than prostacyclin.