ENDOCRINE FUNCTIONS OF THE PLACENTA

拟议的研究解决了普遍的假设，即在先兆子痫患者中， 一种妊娠期高血压疾病，是导致 早产和胎儿生长迟缓，都有异常 胎盘产生过氧化脂质和血管活性二十烷类化合物，以及 这些异常导致的临床症状 高血压、蛋白尿和子宫胎盘减少等疾病 血液流动。拟议的研究解决了胎盘 降压药前列环素(PGl2)的产生减少， 血栓烷(TX)是一种高血压药物，在 先兆子痫。先兆子痫患者胎盘TX产生增加可能是 再加上胎盘中过氧化脂质的分泌增加。脂类 过氧化物质会破坏细胞膜，因此过氧化脂质水平升高 可能与血管内皮细胞损伤和PG12降低有关 先兆子痫。胎盘将从正常怀孕的妇女和 患有先兆子痫的妇女。胎盘组织将被孵化或灌流 体外研究产生率、分泌率和调节 各种因素。二十烷类化合物将通过特定的放射免疫分析和 谷胱甘肽过氧化物酶/还原酶氧化NADPH和 丙二醛生成。具体目标是确定：i) 人胎盘和胎盘中毒素和过氧化脂质的区划 滋养层细胞对它们的产生率的控制 环氧合酶在正常妊娠和子痫前期妊娠中的作用 羟基二十碳四烯酸(HETE)生产的区划 胎盘可以解释胎盘血栓素对滋养细胞的抑制作用； 3)与失衡有关的胎盘血管收缩机制 TX和PG12之间以及脂质过氧化水平的增加。

The proposed studies address the general hypothesis that in preeclampsia, a hypertensive disease of pregnancy that is a leading cause of indicated premature delivery and fetal growth retardation, there is abnormal placenta production of lipid peroxides and vasoactive eicosanoids, and that these abnormalities contribute to the clinical symptoms of the disorder, such as hypertension, proteinuria and reduced uteroplacental blood flow. The proposed studies address mechanisms whereby placenta production of prostacyclin (PGl2), a hypotensive agent, is decreased and that of thromboxane (TX), a hypertensive agent, is increased in preeclampsia. Increased placental TX production in preeclampsia could be coupled to an increase in placenta secretion of lipid peroxides. Lipid peroxides can damage cell membranes, so elevated levels of lipid peroxides could be related to endothelial cell injury and decreased PG12 in preeclampsia. Placentas will be obtained from normally pregnant women and women with preeclampsia. Placental tissues will be incubated or perfused in vitro to study production rates, secretion rates and regulatory factors. Eicosanoids will be measured by specific radioimmunoassays and lipid peroxides by glutathione peroxidase/reductase oxidation of NADPH and malondialdehyde generation. The specific aims are to determine: i) The compartmentalizatlon of TX and lipid peroxides in the human placenta and the control of their production rates by the trophoblast and cyclooxygenase enzyme in normal and preeclamptic pregnancies; 2) Whether compartmentalization of hydroxyeicosatetraenoic acid (HETE) production in the placenta can explain trophoblast inhibition of placental thromboxane; 3) Mechanisms for placenta vasoconstriction relating to an imbalance between TX and PG12 and increased levels of lipid peroxides.