卵巢过度刺激综合征（OHSS）是辅助生殖最具潜在危险的并发症，而导致其发生的机理仍不甚明确。VEGF表达上调导致血管通透性增加是OHSS发生的重要原因。而LncRNA在OHSS发生中的作用尚不明确。那LncRNA是否可能通过调控VEGF导致OHSS发生？机制是什么？前期结果显示：LncRNA GAS5在OHSS高风险患者颗粒细胞中显著下调，生信分析发现GAS5可以和miR-135a-5p结合并靶向FOXO1，而FOXO1调控VEGF通路已有文献报道。基于此我们提出科学假设：GAS5通过结合miR-135a-5p拮抗其对FOXO1的负调控作用，激活并上调VEGF表达并导致OHSS发生。本项目拟从细胞实验、临床及动物模型出发并结合慢病毒，siRNA等工具阐述GAS5/miR-135a-5p调控VEGF通路在颗粒细胞增殖及凋亡中功能和调控机制。从而为OHSS早期预测及治疗靶点选择提供科学依据。

Ovarian hyperstimulation syndrome (OHSS) is the most common and potentially dangerous complication of assisted reproductive technology (ART) and the underlying mechanism is still unclear. It has been well established that elevated VEGF expression leads to an increase in vascular permeability and it is an important cause of OHSS. However, the role of LncRNA in the occurrence of OHSS is dismal. Then whether LncRNA may cause OHSS by regulating VEGF and what is the mechanism? Our previous results showed that LncRNA GAS5 was down-regulated in granulosa cells with OHSS high risk patients and GAS5 could bind to miR-135a-5p which can target to FOXO1 using sequencing and bioinformatics analysis. In addition, FOXO1 can regulate VEGF signal pathway. Based on the results we propose that GAS5 antagonizes its negative regulation of FOXO1 by binding to miR-135a-5p, activating and up-regulating VEGF expression and leading to OHSS. The aim of this project is to reveal the underlying mechanism of GAS5/miR-135a-5p/FOXO1 axis which regulates granulosa cell proliferation and apoptosis via VEGF signal pathway by means of cell, clinical and animal experiments, combined with lentivirus and siRNA. Our study may shed lights to provide scientific basis for early prediction and treatment target selection of OHSS.