A placental phenotype for intrahepatic cholestasis of pregnancy
A placental phenotype for intrahepatic cholestasis of pregnancy
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DOI：
10.1016/j.placenta.2011.09.006
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发表时间：
2011-12-01
期刊：
影响因子：
3.8
通讯作者：
Williamson, C.
中科院分区：
文献类型：
--
作者：
Geenes, V. L.;Lim, Y. -H.;Williamson, C.
妊娠期肝内胆汁淤积 (ICP) 是一种妊娠特异性肝脏疾病，与胎儿并发症的显着风险相关。据推测，胎儿不良结局的风险与胆汁酸的毒性作用有关，母体和胎儿血清中胆汁酸的水平都会增加。人类和啮齿动物研究表明，ICP 中胆汁酸的经胎盘转移受到损害。此外，ICP啮齿动物模型的胎盘形态明显异常，并与细胞凋亡标志物表达增加和氧化应激有关。使用 ICP 病例和正常妊娠的胎盘组织以及培养的胎盘外植体碎片，我们研究了胆汁淤积的组织学和分子效应。我们还研究了熊去氧胆酸（UDCA）给药对这些参数的影响。在这里，我们报告ICP与胎盘的几种形态异常有关，包括合胞结数量的增加，并且这些可以在暴露于胆汁酸牛磺胆酸和牛磺鹅去氧胆酸的体外（外植体）模型中复制。此外，我们证明熊去氧胆酸（一种常用于治疗ICP的药物）在体内和体外对胎盘组织具有保护作用。 (C) 2011 Elsevier Ltd. 保留所有权利。
Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy specific liver disease associated with significant risk of fetal complications. It is hypothesised that the risk of adverse fetal outcomes relates to the toxic effects of bile acids, the levels of which are increased in both maternal and fetal serum. Human and rodent studies have shown that transplacental transfer of bile acids is impaired in ICP. Furthermore, the morphology of placentas from the rodent model of ICP is markedly abnormal, and is associated with increased expression of apoptotic markers and oxidative stress. Using placental tissue from ICP cases and normal pregnancies and cultured placental explant fragments we investigated the histological and molecular effects of cholestasis. We also examined the influence of ursodeoxycholic acid (UDCA) administration on these parameters. Here we report that ICP is associated with several morphological abnormalities of the placenta, including an increase in the number of syncytial knots, and that these can be reproduced in an in vitro (explant) model exposed to the bile acids taurocholic acid and taurochenodoexycholic acid. Furthermore, we demonstrate that ursodeoxycholic acid, a drug commonly used in the management of ICP, has a protective effect on placental tissue both in vivo and in vitro. (C) 2011 Elsevier Ltd. All rights reserved.