合体滋养细胞微泡在树突状细胞介导的子痫前期免疫失衡中的作用及机制研究

Preeclampsia (PE) is an important obstetrical disease posing a serious threat to maternal and fetal health. Dendritic cell (DC) posited in the center of immune regulation, its overavtivity leads to serious immune imbalance and inflammatory responses, which is an important pathogenetic mechanism of PE. The syncytiotrophoblast microvesicle (STBM) in maternal peripheral blood is a significant factor in the pathogenesis of PE, possibly by regulating the activation of DC in the maternal immune response, but the definite mechanism is not clear. This project, based on previous study, will first identify the molecular features and cytological process of DC activation induced by STBM in patients with PE; and then investigate the effects of STBM on differentiation, maturation and response capabilities of DC; afterthat in the placental tissue culture platform of PE late pregnancy, extracting the defective STBM by RNA interference, study the molecular type and mode of action on the surface of STBM that can activate DC; finally, utilize our research group established "C57 mouse PE model basing on STBM" combining in vivo slow virus targeting gene silencing technology as well as STBM in vivo tracer technology to validate the scientific hypothesis that STBM induces maternal immune imbalance in PE through DC activation" and to clarify its possible mechanism. This will provide the feasible target and direct experimental evidence for the new immunological treatment of PE.

子痫前期（PE）是严重威胁孕产妇和胎儿健康的重要产科疾病，处于免疫调节中心环节的树突状细胞（DC）过度活化导致严重免疫失衡和炎症反应是PE的重要发病机制。母体外周血中的合体滋养细胞微泡（STBM）是PE发病的重要因子，可以通过活化DC参与母体免疫反应的调节，但具体机制不清。本项目拟在既往研究基础上，首先明确PE患者STBM导致DC活化的细胞学过程和分子特点；然后了解STBM对DC的成熟、分化和活性状态的影响；随后在PE晚孕胎盘组织培养平台上，运用基因干扰技术提取缺陷型STBM，研究STBM表面活化DC的分子类型和作用方式；最后利用本研究小组前期建立的"基于STBM的C57小鼠PE模型"结合慢病毒在体靶向基因沉默技术和STBM在体示踪技术验证"STBM通过活化DC诱发PE母体免疫失衡"的科学假设、明确其可能的机制，为新的PE免疫学治疗提供可行靶点和直接实验依据。

子痫前期（PE）是严重威胁孕产妇和胎儿健康的重要产科疾病，处于免疫调节中心环节的树突状细胞（DC）过度活化导致严重免疫失衡和炎症反应是PE的重要发病机制。母体外周血中的合体滋养细胞微泡（STBM）是PE发病的重要因子，可以通过活化DC参与母体免疫反应的调节，但具体机制不清。本项目在既往研究基础上，首先明确PE患者STBM导致DC活化的细胞学过程和分子特点；并深入研究了STBM对DC的成熟、分化和活性状态的影响；随后在PE晚孕胎盘组织培养平台上，运用基因干扰技术提取缺陷型STBM，研究STBM表面活化DC的分子类型和作用方式，为新的PE免疫学治疗提供了可行靶点和直接实验依据。通过给正常小鼠注射浓度较高的合体滋养细胞外囊泡构建了基于STBM的妊娠期高血压疾病的动物模型，并获得专利，对深入研究人类子痫的病因、发生发展机制和治疗，具有非常重要的意义。