子痫前期(PE)是妊娠期常见疾病，目前尚缺乏有效治疗方法。研究证实VEGF与KDR结合减少而VEGF与sFlt-1结合增加是导致PE的主要原因；因此，VEGF-KDR/sFlt-1通路成为PE治疗的靶点。RNA激活(RNAa)是最近发现的一种新分子现象：小激活RNA(saRNA)可以靶向目的基因启动子区，持续有效上调目的基因的表达。我们拟将RNAa和现有的RNA干扰技术相结合，通过saRNA靶向激活VEGF表达并下调sFlt-1表达，持续有效的活化VEGF-KDR通路，抑制VEGF-sFlt-1通路，从而通过促进NO分泌、减少ROS等逆转PE病理生理改变。同时利用安全且对胎儿影响小的G4-PAMAM纳米颗粒搭载VEGF-saRNA和sFlt-1-siRNA，在PE动物模型上验证该纳米复合物通过双靶向调控VEGF-KDR/sFlt-1信号通路对PE的治疗作用，以期找到PE基因治疗的新方法。

Preeclampsia is an extremely common pregnancy complication, which is still eager for effective therapies. Existing researches have confirmed that increased binding of VEGF to sFlt-1 and decreased binding of VEGF to KDR are the major pathological mechanisms of PE. Thus, both VEGF and sFlt-1 are therapeutic targets of PE. RNA activation (RNAa) is a new mechanism of gene regulation. Special small activating RNAs are designed to targeting promoter regions, which could sustained activate the expression of target genes. This study intends to utilize RNAa and RNAi to activate VEGF and silence sFlt-1 separately, thereby sustained activate VEGF-KDR signaling pathway, and suppress VEGF-sFlt-1 signaling pathway, and subsequently promote secretion of nitric oxide and decrease oxidative damage. Furthermore, we also intends to use G4-PAMAM dendrimer, which is a nanocarrier with non-toxic and little effect on the fetus, to co-deliver VEGF-saRNA and sFlt-1-siRNA into preeclamptic rats, and then in vivo analyze the therapeutic effect of VEGF-saRNA-sFlt-1-siRNA-G4-PAMAM dendrimer on PE. Our study may finally demonstrate an effective therapeutic method for gene therapy of PE.