子痫前期（PE）在我国孕产妇人群中有高发病率和高致死率。氧化应激在PE发病中起重要作用，但其调节机制尚未阐明。PE人群中存在RND3基因单核苷酸多态性，推测RND3表达在PE中有潜在临床意义。我们前期研究发现1）RND3在PE人胎盘中表达下调，伴随氧化应激和线粒体损伤；2）细胞实验表明Rnd3调控线粒体功能和活性氧簇产生；3）microarray进一步证实Rnd3下调导致线粒体损伤；4）Rnd3免疫共沉淀产物进行质谱分析，揭示线粒体外膜转运酶亚基TOM40与Rnd3结合。据此假设：Rnd3与TOM40相互作用调控线粒体功能，实现对PE氧化应激机制的调控。本研究拟采用CRISPR技术建立细胞模型，RUPP手术和条件性基因敲除建立动物模型，从细胞-个体-分子层面探索Rnd3介导的线粒体功能调节参与PE发病的机制。研究结果将揭示Rnd3在调控PE氧化应激的重要作用，为发展新的干预手段提供新思路。

Preeclampsia (PE) is a life-threaten disease among the population of pregnant women in China with high morbidity and high mortality. Oxidative stress has been suggested involving the pathogenesis of PE with uncovered the molecular mechanism. A study has reported the RND3 SNP in the population with PE, which indicated the clinical significance of RND3 in PE. Our preliminary studies found that 1) the expression of RND3 was down-regulated in the human placenta of PE patients along with increased oxidative stress and mitochondrial dysfunction; 2) our in vitro study showed that Rnd3 modulated mitochondrial function and ROS generation; 3) the microarray data further demonstrated that the down-regulation of Rnd3 results in mitochondrial dysfunction; 4) the analysis of pull-down experiment showed that Rnd3 could directly bind to TOM40, which is the core subunit of mitochondrial outer membrane translocase complex (TOM). Therefore, our central hypothesis is Rnd3 modulates preeclampsia by regulating mitochondrial function and oxidative stress via its directly bound with TOM40. We proposed to generate the CRISPR/Cas9 KO cell line, the RUPP surgery induced PE mouse model and conditional knock-out mouse model to investigate the role of Rnd3 mediated mitochondrial dysfunction in PE pathogenesis. Our study will reveal the critical role of Rnd3 in the pathogenesis of PE, and provide new angle to develop treatment for PE.