PE严重威害母儿安全，治疗中存在尖锐的母胎利益冲突，EVT侵袭力下降是该病发生的关键环节，具体分子机制不清。研究证实，miRNAs可通过靶基因调控EVT功能，在PE发生发展中发挥作用。但绝大多数miRNAs的功能和调控机制尚不清楚。申请人研究发现，PE胎盘中miR-513c-5p表达上调，LRP6表达下调；又证实，EVT中miR-513c-5p可靶向抑制LRP6表达，而LRP6表达下调可致EVT功能受损。项目拟进一步验证miR-513c-5p对LRP6的靶向调控作用，阐明其与EVT侵袭力下降和PE发病的关系。项目还将尝试构建纳米载体plCSA-LPH-NPs，靶向输送miR-513c-5p反义核酸进入EVT，下调miR-513c-5p，上调LRP6表达，改善EVT功能，治疗PE。将为进一步认识PE发病机制提供新的理论依据，为核酸药物、纳米载体等技术方法在PE靶向治疗领域的应用提供实践基础。

Preeclampsia (PE) is a serious pregnant complication, and there are sharp conflicts of interest between mother and fetus in the treatment. Its specific molecular mechanism is unclear, and declined invasion of extravillous trophoblast (EVT) is a key point. MiRNAs can regulate EVT function through their target genes, and play an important role in the development of PE. However, the functions and regulatory mechanisms of most miRNAs are still unclear. Our preliminary study found that the expression of mir-513c-5p was up-regulated, while the expression of LRP6 was down-regulated in the PE placentas. And it was confirmed in EVT that mir-513c-5p can targeted inhibit the expression of LRP6, while the down-regulation of LRP6 can lead to the impairment of EVT function. The project intends to further verify the targeted regulatory effects of mir-513c-5p on LRP6, and clarify their relationship with the decline of EVT invasiveness and the development of PE. The project will also attempt to construct plCSA-LPH-NPs nanoparticular (NP) system to deliver mir-513c-5p antisense oligonucleotide (ASO) into EVT, down-regulate mir-513c-5p, up-regulate LRP6 expression, improve EVT function and treat PE. We wish the results can provide a new theoretical basis for further understanding the pathogenesis of PE, and provide a practical basis for the application of nucleic acid drugs, NPs and other technical methods in the field of PE targeted therapy.