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正常妊娠和高血压妊娠的人胎盘中内皮素-1样免疫反应性及内皮素受体

Endothelin-1-like immunoreactivity and endothelin receptors in the human placenta from normotensive and hypertensive pregnancies.

作者信息

Hasegawa M, Sagawa N, Nanno H, Itoh H, Inamori K, Ihara Y, Kobayashi F, Mori T, Yano J, Shirakami G, Suga S, Ogawa Y, Yoshimasa T, Nakao K

机构信息

Department of Obstetrics and Gynecology, Kyoto University, Faculty of Medicine, Japan.

出版信息

J Perinat Med. 1996;24(5):451-60. doi: 10.1515/jpme.1996.24.5.451.

DOI:10.1515/jpme.1996.24.5.451
PMID:8950725
Abstract

The levels of endothelin-1-like immunoreactivity (ET-1-LI) and characteristics of endothelin receptors in the chorionic villous tissue of human placenta were determined. The ET-1-LI level in chorionic villous tissue obtained from normal term placenta was 2,450 +/- 940 pg/g wet weight (mean +/- SD, n = 4). Further analysis using gel permeation chromatography and reverse-phase high performance liquid chromatography showed that the main ET-1-LI constituent of ET-1-LI in this tissue was ET-1. Scatchard analysis of [125I]ET-1 binding to the membrane fraction of chorionic villous tissue obtained from term placenta showed high affinity receptor sites with an apparent dissociation constant (Kd) of 23.6 +/- 11.1 pM and a Bmax value of 388 +/- 238 fmol/mg protein (n = 5). The same binding study with [125I]ET 3 showed a Kd of 13.9 +/- 3.8 pM and a Bmax value of 176 +/- 78 fmol/mg protein (n = 5). These results suggest that both ET-A and ET-B receptors (ET-AR and ET-BR) are expressed in chorionic villous tissue. This finding was further confirmed by Northern blot analysis showing the expression of both ET-AR and ET-BR mRNAs in this tissue. ET-1-LI in the umbilical venous plasma of the newborns from women with pregnancy-induced hypertension (PIH) (38.3 +/- 10.4 pg/mL, n = 5) was significantly (P < 0.05) higher than that in the normal newborns from normotensive pregnant women (26.3 +/- 5.2 pg/mL, n = 12). However, in placental chorionic villous tissue obtained from PIH women, both ET-1-LI level and ET binding profile were not different from those in chorionic villous tissue from normotensive pregnant women. These results suggest that the abundant ET-ET receptor system is present in the placental chorionic villous tissue and that this system is not the major factor of the pathogenesis of placental dysfunction occurring in PIH because these systems are similar in normotensive and hypertensive pregnancies.

摘要

测定了人胎盘绒毛膜组织中内皮素-1样免疫反应性(ET-1-LI)水平及内皮素受体特征。从足月正常胎盘获取的绒毛膜组织中ET-1-LI水平为2450±940 pg/g湿重(均值±标准差,n = 4)。采用凝胶渗透色谱和反相高效液相色谱进一步分析表明,该组织中ET-1-LI的主要成分是ET-1。对[¹²⁵I]ET-1与足月胎盘绒毛膜组织膜部分结合进行Scatchard分析显示,存在高亲和力受体位点,其表观解离常数(Kd)为23.6±11.1 pM,最大结合容量(Bmax)值为388±238 fmol/mg蛋白质(n = 5)。用[¹²⁵I]ET-3进行的相同结合研究显示,Kd为13.9±3.8 pM,Bmax值为176±78 fmol/mg蛋白质(n = 5)。这些结果提示,ET-A和ET-B受体(ET-AR和ET-BR)均在绒毛膜组织中表达。Northern印迹分析显示该组织中ET-AR和ET-BR mRNA均有表达,进一步证实了这一发现。妊娠高血压综合征(PIH)孕妇所生新生儿脐静脉血浆中的ET-1-LI(38.3±10.4 pg/mL,n = 5)显著高于(P<0.05)血压正常孕妇所生正常新生儿(26.3±5.2 pg/mL,n = 12)。然而,从PIH孕妇获取的胎盘绒毛膜组织中,ET-1-LI水平和ET结合情况与血压正常孕妇的绒毛膜组织并无差异。这些结果提示,胎盘绒毛膜组织中存在丰富的内皮素-内皮素受体系统,且该系统并非PIH中发生胎盘功能障碍的主要发病因素,因为在血压正常和高血压妊娠中这些系统是相似的。

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