He W-Y, Chen G-J, Lai X, Wu F, Tang C-S, Zhang A-H
Department of Nephrology, Peking University Third Hospital, Beijing, China.
Department of Pathology and Physiology, Peking University Health Science Center, Beijing, China.
J Hum Hypertens. 2016 Feb;30(2):129-35. doi: 10.1038/jhh.2015.28. Epub 2015 Apr 16.
Hypertensive disorders in pregnancy remain a leading cause of maternal and perinatal mortality and morbidity. We aim to study urotensin II (UII) and its association with the markers of endoplasmic reticulum stress (ERS) in placentas of patients with severe preeclampsia (SPE). Thirty-three patients with hypertensive disorders in pregnancy and twenty-two healthy pregnant women designated as healthy controls were recruited. Expression levels of UII, UII receptor (GPR14) and the markers of ERS in placenta specimens of patients were performed. Plasma and urinary UII levels were measured by radioimmunoassay method. Our study showed that the plasma levels of UII in patients with hypertensive disorders during pregnancy were significantly higher than that of the healthy control group. However, the urinary levels of UII had no difference in two groups. The expression level of mRNA and protein of UII, CCAAT/enhancer-binding protein homologous protein (CHOP) and glucose regulation protein 78 in placentas of SPE was significantly increased. Immunohistochemical analyses show that the expression levels of UII and ERS markers were mainly located in the cytoplasm of placental trophoblastic cells. Moreover, expression level of UII mRNA and protein was positively correlated with that of the markers of ERS. The positive correlation between UII and ERS markers expression level also corresponded with the level of patient's systolic blood pressure and proteinuria. In conclusion, we first verify that expression of UII is associated with ERS in patients with SPE. Our results indicate that UII may trigger ERS in placental trophoblastic cells in patients with preeclampsia.
妊娠期高血压疾病仍然是孕产妇和围产儿发病和死亡的主要原因。我们旨在研究尿紧张素II（UII）及其与重度子痫前期（SPE）患者胎盘内质网应激（ERS）标志物的关系。招募了33例妊娠期高血压疾病患者和22名健康孕妇作为健康对照。检测了患者胎盘标本中UII、UII受体（GPR14）及ERS标志物的表达水平。采用放射免疫分析法测定血浆和尿液中的UII水平。我们的研究表明，妊娠期高血压疾病患者的血浆UII水平显著高于健康对照组。然而，两组的尿液UII水平无差异。SPE患者胎盘中UII、CCAAT/增强子结合蛋白同源蛋白（CHOP）和葡萄糖调节蛋白78的mRNA和蛋白表达水平显著升高。免疫组化分析显示，UII和ERS标志物的表达水平主要位于胎盘滋养层细胞的细胞质中。此外，UII mRNA和蛋白的表达水平与ERS标志物的表达水平呈正相关。UII与ERS标志物表达水平的正相关也与患者的收缩压和蛋白尿水平相对应。总之，我们首次证实SPE患者中UII的表达与ERS有关。我们的结果表明，UII可能在子痫前期患者的胎盘滋养层细胞中引发ERS。
