TFPI-2基因在子痫前期发病机制中的作用

项目名称： TFPI-2基因在子痫前期发病机制中的作用

项目编号： No.30872777

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 生物科学

项目作者： 李笑天

作者单位： 复旦大学

项目金额： 31万元

中文摘要： 本项目从组织、细胞以及基因剔除动物模型三个层面研究TFPI-2在子痫前期发病机制中的作用。应用ELISA和免疫组化方法分析母儿血清和胎盘中TFPI-2的表达变化，发现子痫前期孕妇血清TFPI-2水平降低减少，胎盘表达增加；采用转染技术调控滋养细胞株中TFPI-2表达研究对滋养细胞生物学功能的影响，发现TFPI-2表达抑制滋养细胞增殖和侵袭能力，促进其凋亡，对分化能力无明显影响；运用基因剔除方法成功建立条件性TFPI-2敲除小鼠，选用iNOS和ApoE敲除小鼠，发现APOE可能具有降低血压和蛋白尿的作用，iNOS具有减少蛋白尿的作用，两者对滋养细胞形态维持有作用，对血脂无明显影响。本项目在临床水平发现TFPI-2在子痫前期中异常表达，在细胞水平分析TFPI-2对滋养细胞功能的调控，并从动物水平阐明TFPI-2在子痫前期发病机制中的作用。

中文关键词： 组织因子途径抑制物-2；子痫前期；滋养细胞；基因敲除

英文摘要： In this project, we investigated the role of TFPI-2 in preeclampsia by the clinical, celluar and animial approaches. Firstly, it was showed that TFPI-2 decreased in maternal serum and increased in placenta in the detection of TFPI-2 expression by ELISA and histochemistry. Secondly, using plasmid and siRNA transfection, we found that TFPI-2 expression inhibited the proliferation and invasion of trophoblast, induced apoptosis and had no significant effect on differenciation. Thirdly, conditional TFPI-2 knock-out mouse was successfully established. In iNOS and ApoE knock-out mice, it was demonstrated that APOE possibly decreased hypertension and proteinuria while iNOS decreased proteinuria; also, APOE and iNOS may have effects on the maintenance of trophoblast pattern and have no effect on lipid. In conclusion, this study suggested possible role of TFPI-2 in causing impaired trophoblast invasion in the etiology of preeclampsia.

英文关键词： tissue factor pathway inhibitor-2; preeclampsia; trophoblast; knock-out