Placental isoprostane is significantly increased in preeclampsia
Placental isoprostane is significantly increased in preeclampsia
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DOI：
10.1096/fj.14.10.1289
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发表时间：
2000-07-01
期刊：
影响因子：
4.8
通讯作者：
Roberts, LJ
中科院分区：
文献类型：
--
作者：
Walsh, SW;Vaughan, JE;Roberts, LJ
我们测定了正常妊娠妇女和先兆子痫（一种妊娠期高血压疾病）妇女的胎盘组织中异前列腺素的水平、产生率和分泌率。异前列腺素是氧化应激的标志物，其发挥生物学作用，例如血管收缩。冲洗胎盘组织并立即在液氮中冷冻，以测定总异前列烷和游离异前列烷的组织水平。还将胎盘组织块在无血清DMEM中在37 ℃、95%空气/5%CO2中孵育48小时，以确定生产速率。灌注分离的胎盘子叶以测定分泌速率。使用8-Iso-PGF（2）（15-F-2 t-IsoP）特异性抗体通过EIA分析所有样品的异前列烷。此外，还分析了培养基样品的丙二醛（MDA），这是一种脂质过氧化的分解产物。我们发现，游离异前列烷和总异前列烷（游离加酯化形式）的组织水平显着高于先兆子痫胎盘比正常胎盘。培养液中异前列腺素和MDA的浓度在48 h内逐渐升高。在48 h内，先兆子痫孕妇胎盘中异前列腺素和MDA的平均浓度均显著高于正常孕妇胎盘。MDA浓度与异前列腺素浓度高度相关。用黄嘌呤加黄嘌呤氧化酶诱导氧化应激增加了正常组织的异前列腺素胎盘产量，达到与先兆子痫组织相似的水平。胎盘分泌的异前列烷是8倍更大的朝向母体侧的胎盘比朝向胎儿侧，并增加了6倍的母体侧和2倍的胎儿侧诱导氧化应激与叔丁基过氧化氢。这项研究提供了新的信息，异前列腺素是由人类胎盘形成和分泌的，并提供了令人信服的证据，氧化应激和脂质过氧化异常增加，在先兆子痫妇女的胎盘。
We determined placental tissue levels, production rates, and secretion rates of isoprostanes for placentas obtained from women with normal pregnancies and women with preeclampsia, a hypertensive disorder of pregnancy. Isoprostanes are markers of oxidative stress that exert biological actions such as vasoconstriction. Placental tissue was rinsed and immediately frozen in liquid nitrogen to determine tissue levels of total and free isoprostane. Placental tissue pieces were also incubated in serum-free DMEM for 48 h at 37 degrees C in 95% air/5% CO2 to determine production rates. Isolated placental cotyledons were perfused for the determination of secretion rates. All samples were analyzed by EIA for isoprostane using an antibody specific for 8-Iso-PGF(2) (15-F-2t-IsoP). In addition, medium samples were analyzed for malondialdehyde (MDA), a breakdown product of lipid peroxidation. We found that tissue levels of free isoprostane and total isoprostane (free plus esterified forms) were significantly higher for preeclamptic placentas than for normal placentas. Concentrations of isoprostane and MDA in the medium increased progressively during 48 h of incubation of placental explants, At 48 h of incubation, the mean concentrations of both isoprostane and MDA were significantly higher for the placentas from preeclamptic women than for the placentas from normal pregnant women. Concentrations of MDA were highly correlated with those of isoprostane. Induction of oxidative stress with xanthine plus xanthine oxidase increased placental production of isoprostane by normal tissue to a level similar to that of preeclamptic tissue. Placental secretion of isoprostane was eightfold greater toward the maternal side of the placenta than toward the fetal side, and was increased sixfold on the maternal side and twofold on the fetal side by inducing oxidative stress with t-butyl hydroperoxide. This study presents new information that isoprostanes are formed and secreted by the human placenta and provides convincing evidence that oxidative stress and lipid peroxidation are abnormally increased in placentas of preeclamptic women.