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子痫前期女性的血清可诱导内皮细胞单层通透性增加,但正常妊娠女性或未孕女性的血清则不会。

Increased endothelial monolayer permeability is induced by serum from women with preeclampsia but not by serum from women with normal pregnancy or that are not pregnant.

作者信息

Zhang Yanping, Gu Yang, Li Hui, Lucas Michael J, Wang Yuping

机构信息

Obstetrics and Gynecology Department, Louisiana State University Health Sciences Center, Shreveport, Lousiana 71130, USA.

出版信息

Hypertens Pregnancy. 2003;22(1):99-108. doi: 10.1081/PRG-120017008.

DOI:10.1081/PRG-120017008
PMID:12648447
Abstract

OBJECTIVE

To determine if endothelial monolayer permeability could be altered by serum from preeclampsia (PE).

METHODS

Confluent normal endothelial cells (ECs) were incubated with 20% serum from nonpregnant females, normal and PE pregnancies or combined with antioxidant superoxide dismutase (SOD) for 8 hr. Confluent PE ECs were incubated with 20% serum from normal pregnancies. EC barrier function of monolayer permeability was accessed by measuring EC electrical resistance (ER) and the leakage of horseradish peroxidase (HRP) passing through EC filters. Plasma concentrations of IL-8 and lipid peroxides by MDA were also measured. We determined 1) if serum from PE could affect EC permeable function; 2) if antioxidant and serum from normal pregnancies could preserve PE EC barrier function; 3) if lipid peroxides and cytokine IL-8 were increased in PE blood samples. Data are presented as mean+/-SE. ANOVA was used for statistical analysis. A p level less than 0.05 was considered statistically different.

RESULTS

  1. ER was significantly decreased and HRP passage was significantly increased in ECs incubated with serum from PE compared to serum from non-pregnant and normal pregnant females (ER: 36.30+/-2.60 vs. 51.30+/-4.00 and 53.90+/-5.80 Omega x cm2, p<0.01; HRP: 0.100+/-0.020 vs. 0.014+/-0.002 and 0.022+/-0.007 DeltaOD470 nm, p<0.01, respectively). 2) ER was improved in PE ECs incubated with serum from normal pregnancies compared to controls, 52.28+/-3.13 vs. 34.50+/-3.80 Omega x cm2, p<0.01. 3) SOD attenuated decreased EC ER induced by PE serum, 55.58+/-3.61 Omega x cm2 (SOD+PE serum) vs. 42.34+/-3.24 (control) and 35.46+/-2.44 (PE serum), p<0.01, respectively. 4) Both MDA and IL-8 concentrations were higher in plasma or serum samples from PE than those in samples from nonpregnancies and normal pregnancies, MDA: 28.65+/-1.45 vs. 22.40+/-1.47 and 25.53+/-0.89 micromol/mL, p<0.01; IL-8: 5.35+/-1.08 vs. 1.69+/-0.47 and 2.28+/-0.73 pg/mL, p<0.05, respectively. Conclusions. 1) Sera from PE but not from nonpregnant women or normal pregnancies increase EC monolayer permeability. 2) Increased lipid peroxides and IL-8 are candidates altering EC barrier function. 3) Antioxidant SOD preserves increased EC monolayer permeability induced by PE serum, suggesting that EC oxidative stress may be associated with altered EC barrier function in preeclampsia.
摘要

目的

确定子痫前期(PE)患者血清是否会改变内皮细胞单层通透性。

方法

将融合的正常内皮细胞(ECs)与来自未孕女性、正常妊娠和PE妊娠的20%血清孵育,或与抗氧化剂超氧化物歧化酶(SOD)联合孵育8小时。将融合的PE内皮细胞与来自正常妊娠的20%血清孵育。通过测量内皮细胞电阻(ER)和辣根过氧化物酶(HRP)透过内皮细胞滤膜的渗漏情况来评估单层通透性的内皮细胞屏障功能。还测量了血浆中IL-8浓度和丙二醛(MDA)表示的脂质过氧化物水平。我们确定了:1)PE患者血清是否会影响内皮细胞的通透功能;2)抗氧化剂和正常妊娠血清是否能维持PE内皮细胞的屏障功能;3)PE血样中脂质过氧化物和细胞因子IL-8是否升高。数据以平均值±标准误表示。采用方差分析进行统计分析。p值小于0.05被认为具有统计学差异。

结果

1)与未孕和正常妊娠女性血清孵育的内皮细胞相比,与PE患者血清孵育的内皮细胞ER显著降低,HRP通过率显著增加(ER:36.30±2.60 vs. 51.30±4.00和53.90±5.80Ω×cm2,p<0.01;HRP:0.100±0.020 vs. 0.014±0.002和0.022±0.007ΔOD470 nm,p<0.01)。2)与对照组相比,与正常妊娠血清孵育的PE内皮细胞ER有所改善,52.28±3.13 vs. 34.50±3.80Ω×cm2,p<0.01。3)SOD减弱了PE血清诱导的内皮细胞ER降低,55.58±3.61Ω×cm2(SOD+PE血清)vs. 42.34±3.24(对照组)和35.46±2.44(PE血清),p<0.01。4)PE患者血浆或血清样本中MDA和IL-8浓度均高于未孕和正常妊娠样本,MDA:28.65±1.45 vs. 22.40±1.47和25.53±0.89μmol/mL,p<0.01;IL-8:5. .35±1.08 vs. 1.69±0.47和2.28±0.73 pg/mL,p<0.05。结论:1)PE患者血清而非未孕女性或正常妊娠血清会增加内皮细胞单层通透性。2)脂质过氧化物和IL-8升高可能是改变内皮细胞屏障功能的因素。3)抗氧化剂SOD可维持PE血清诱导的内皮细胞单层通透性增加,提示内皮细胞氧化应激可能与子痫前期内皮细胞屏障功能改变有关。

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