Yang Xiao, Ding Yi-Ling
Department of Obstetrics and Gynecology, Xiangya Second Hospital, Central South University, Changsha 410011, China.
Zhonghua Fu Chan Ke Za Zhi. 2008 Feb;43(2):85-9.
To investigate the changes of umbilical cord and the vasoactive substance in umbilical vein in intrahepatic cholestasis of pregnancy.
By HE staining method we analyzed the pathologic change of umbilical cord of 25 women with intrahepatic cholestasis of pregnancy (ICP) and fetal distress (ICP fetal distress group), 25 ICP women without fetal distress group (ICP control group) and 27 normal pregnancies (control group). The nitric oxide synthase (NOS) and endothelin-1 (ET-1) were detected in human umbilical vein endothelial cells (HUVEC) by immunohistochemistry method. Umbilical vein total bile acid (TBA) and NOS and ET-1 were measured.
(1) A remarkable high TBA level was found in umbilical vein in ICP, and it was higher in ICP fetal distress group (19.0 +/- 2.3) micromol/L than in ICP control group (9.0 +/- 1.7) micromol/L (P < 0.05); it was higher in ICP control group than the control group (4.4 +/- 1.5) micromol/L (P < 0.05). (2) A significant difference was found in the endotheliocytes of umbilical vein in ICP fetal distress group compared with ICP control group. The ratio of cells with pathological changes in ICP fetal distress group (92%, 23/25) was higher than ICP control group (68%, 17/25; P < 0.05). The occurrence of the pathological changes was associated with TBA. (3) The expression of eNOS in ICP fetal distress group 0.09 +/- 0.06 was lower than in ICP control group 0.21 +/- 0.08 (P < 0.05), and it was lower in ICP control group than in control group 0.47 +/- 0.07 (P < 0.05). In contrast, the expression of ET-1 in ICP fetal distress group 0.49 +/- 0.08 was higher than in ICP control group 0.32 +/- 0.07 (P < 0.05), and it was higher in ICP control group than control group 0.14 +/- 0.06 (P < 0.05). The expression of inducible nitric oxide synthase (iNOS) in ICP fetal distress group 0.20 +/- 0.04 and ICP control group 0.21 +/- 0.05 was lower than in control group 0.26 +/- 0.04 (P < 0.05), but no significant difference was found in ICP fetal distress group and ICP control group (P > 0.05). (4) The expression of eNOS, iNOS and ET-1 was correlated with umbilical vein TBA in ICP (r1 = -0.88, r2 = -0.45, r3 = 0.9; P < 0.01), respectively.
High level of TBA in ICP is harmful to the umbilical vein endothelium, which is correlated with the raised expression of ET-1, and the decreased expression of eNOS,and iNOS in human umbilical cord endothelium cells. All these changes of umbilical vein may be associated with the occurrence of fetal distress in ICP.
探讨妊娠肝内胆汁淤积症患者脐带及脐静脉中血管活性物质的变化。
采用HE染色法分析25例妊娠肝内胆汁淤积症合并胎儿窘迫患者（ICP胎儿窘迫组）、25例无胎儿窘迫的妊娠肝内胆汁淤积症患者（ICP对照组）及27例正常妊娠者（对照组）的脐带病理变化。采用免疫组织化学方法检测人脐静脉内皮细胞（HUVEC）中的一氧化氮合酶（NOS）和内皮素-1（ET-1）。检测脐静脉总胆汁酸（TBA）、NOS及ET-1水平。
（1）ICP患者脐静脉TBA水平显著升高，ICP胎儿窘迫组（19.0±2.3）μmol/L高于ICP对照组（9.0±1.7）μmol/L（P＜０.０５）；ICP对照组高于对照组（4.4±1.5）μmol/L（P＜０.０５）。（2）ICP胎儿窘迫组脐静脉内皮细胞与ICP对照组相比有显著差异。ICP胎儿窘迫组病理改变细胞比例（92%，23/25）高于ICP对照组（68%，17/25；P＜０.０５）。病理改变的发生与TBA有关。（3）ICP胎儿窘迫组eNOS表达（0.09±0.06）低于ICP对照组（0.21±0.08）（P＜０.０５），ICP对照组低于对照组（0.47±0.07）（P＜０.０５）。相反，ICP胎儿窘迫组ET-1表达（０.４９±０.０８）高于ICP对照组（０.３２±０.０７）（P＜０.０５），ICP对照组高于对照组（０.１４±０.０６）（P＜０.０５）。ICP胎儿窘迫组诱导型一氧化氮合酶（iNOS）表达（０.２０±０.０４）和ICP对照组（０.２１±０.０５）低于对照组（０.２６±０.０４）（P＜０.０５），但ICP胎儿窘迫组与ICP对照组无显著差异（P＞０.０５）。（4）ICP中eNOS、iNOS及ET-1表达与脐静脉TBA相关（r1=-0.88，r2=-0.45，r3=0.9；P＜０.０１）。
ICP中高水平的TBA对脐静脉内皮有损害，这与ET-1表达升高、人脐带内皮细胞中eNOS及iNOS表达降低有关。脐静脉的所有这些变化可能与ICP中胎儿窘迫的发生有关。
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