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Placental dysfunction and maternal endothelial cell dysfunction in the pathogenesis of preeclampsia

子痫前期发病机制中的胎盘功能障碍和母体内皮细胞功能障碍

基本信息

批准号：
16591666
负责人：
TSUKIMORI Kiyomi
金额：
$ 2.18万
依托单位：
Kyushu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591666/
关键词：
Preeclmusia Placental dysfunction Endothelial cell dysfunction Neutrophil Systemic inflammatory response

项目摘要

The aim of this study was to clarify the relationship between placental abnormalities and the potential cellular mechanisms contributing to the maternal endothelial cell dysfunction in preeclampsia from the viewpoint of neutrophill-endothelial cell interaction.Firstly, we investigated the effect of sera from women with preeclampsia on neutrophils. It was demonstrated that the sera from women with preeclampsia significantly enhance N-formyl-methionyl-leucyl-phenylalanine-induced superoxide production as compared to the sera of normal pregnant women, and that enhanced superoxide production of neutrophils induces the endothelial cell injury. In addition, sera from women with preeclampsia inhibited 3H-thymidine incorporation and reduced cellular viability of cultured trophoblasts. Gel permeation showed that the greatest growth-inhibitory activity corresponded to a molecular weight of 50 kDa. The serum enhanced activity to neutrophils was found in the same fraction of the placental cytotoxic activity.Next, we investigated whether placental ischemia/hypoxia stimulates the production of maternal serum cytotoxic factor(s) using pregnant rats treated with the nitric oxide synthase inhibitor(L-NAME). In L-NAME treated pregnant rats, light microscopy showed that giant cells were decreased in number and spongiotrophoblast layers were degenerated compared to control pregnant rats. Maternal serum cytotoxic activity to placental trophoblasts was present in L-NAME treated pregnant rats. Elevated serum TNF-α levels and increased expression of TNF-α in placental trophoblasts were observed in L-NAME treated pregnant rats.These findings suggest that placental ischemia/hypoxia stimulate the factor(s), such as inflammatory cytokines, that promote several forms of endothelial dysfunction in preeclampsia, and contribute to the substantial risks for developing this disorder during pregnancy

本研究的目的是从中性粒细胞-内皮细胞相互作用的角度阐明先兆子痫患者胎盘异常与母体内皮细胞功能障碍的潜在细胞机制之间的关系。结果表明，与正常孕妇的血清相比，先兆子痫妇女的血清显着增强N-甲酰-甲硫氨酰-亮氨酰-苯丙氨酸诱导的超氧化物的产生，并且中性粒细胞的超氧化物产生的增强诱导内皮细胞损伤。此外，先兆子痫妇女的血清抑制3 H-胸苷掺入和培养的滋养层细胞的细胞活力降低。凝胶渗透表明，最大的生长抑制活性对应于50 kDa的分子量。血清增强活性的中性粒细胞被发现在同一分数的胎盘cytotoxicactivity.Next，我们调查是否胎盘缺血/缺氧刺激母体血清细胞毒性因子（S）的生产使用一氧化氮合酶抑制剂（L-NAME）处理的妊娠大鼠。在L-NAME治疗的孕鼠，光镜下显示，巨细胞的数量减少和海绵滋养层退化相比，对照组孕鼠。L-NAME处理的孕鼠母体血清对胎盘滋养层细胞具有细胞毒活性。L-NAME处理的孕鼠血清TNF-α水平升高，胎盘滋养细胞TNF-α表达增加，提示胎盘缺血缺氧刺激炎症因子等因子，促进子痫前期内皮功能障碍，并增加妊娠期子痫前期的发病风险