子痫前期母胎界面细胞因子网络调节信号研究

Preeclampsia (PE) is one of the major causes of maternal and perinatal morbidity and mortality. Effective markers for early detection of pregnancies that destined to experience preeclampsia is important to estimate their proximity to onset of the clinical disease, and would permit medical care providers to plan more detailed course of action. Decidual Cells, the extravillous trophoblasts, vascular endothelial cells, maternal immune cells,inflammatory cells in maternal fetal interface secret multiple cytokines during different gestational weeks, which interact with each other, thus formulate a complex functional regulated and control network. Cytokine regulated and control network in maternal fetal interface plays a key role in the pathogenesis of preeclampsia. However, studies attempting to demonstrate the interactions between different cells in maternal fetal interface at the macroscopic level are limited. Integrated studies are required to the futher understand the pathogenesis of PE. We proposed to continuously measure the level of cytokines related to PE at different gestational weeks in preeclampsia-like and normal control mouse model. The levels of cytokine produced in PE placenta and normal controls will be measured by ELISA assays, protein chips, mRNA microarrays and real-time PCRs to investigate the cellular mechanisms involved in the development of the disease. Also, we proposed to validate the candidate biomarkers discovered in the mouse model on 40 PE patients and 40 normal human pregnancies. Then, we will evaluate the most promising biomarkers on 400 prospective clinical samples, which may lead to further understanding of the pathogenesis of PE and to predict PE in early trimester.

子痫前期(PE)是最严重的妊娠并发症之一，是导致孕产妇和围产儿死亡的主要原因之一。对子痫前期的早期预测并尽早干预和密切监测可减少和避免不良母婴结局。母胎界面的蜕膜细胞、绒毛外滋养细胞、血管内皮细胞、免疫细胞、炎症细胞在妊娠过程的不同阶段，释放多种不同细胞因子相互作用，形成复杂的功能调控网络，这种调控异常在PE发病机制中起重要作用。本研究以PE小鼠模型与正常妊娠小鼠为研究对象，采用蛋白质芯片和mRNA基因芯片等方法检测外周血、脾脏和胎盘组织中神经内分泌免疫调节网络功能相关信号的表达水平，确定母胎界面相关细胞中PE相关的细胞因子调节网络，及其与机体宏观调节网络的联系，找出PE疾病相关的早期预测分子标记物和干预靶点。临床试验选取PE和正常对照组孕妇各40例，采用相同的方法检测上述指标表达水平，验证其PE相关性。自早孕期开始前瞻性收集400例孕妇并随访妊娠结局，验证这些指标对PE的早期预测价值。