新生儿持续肺动脉高压（PPHN）是NICU最常见的危重症之一，病死率和致残率高。近年遗传因素在PPHN发生中的作用备受关注。低氧诱导因子（HIF）通路是肺动脉高压发生中参与缺氧应答的关键信号通路。在前期研究中，我们发现编码HIF通路中重要氧感受器脯氨酸羟化酶（PHD2）的EGLN1基因变异，可能参与了PPHN的发生。本课题拟进一步：（1）扩大样本量，检测PPHN患儿EGLN1的变异情况，证实EGLN1变异是PPHN发生重要的遗传背景因素；（2）构建内皮细胞特异性EGLN1基因敲除小鼠，并暴露于常氧和低氧状态下，动态监测新生小鼠肺动脉压力和不同时期血管壁病理改变以及HIF通路基因表达情况。初步揭示EGLN1介导的HIF通路在PPHN发生中的重要作用和分子机制，为PPHN的诊治提供新的思路。

Persistent pulmonary hypertension of the newborn (PPHN) is a common critical disease with high mortality and morbidity in newborn nursery. Genetic factors have been recognized to be involved in the development of PPHN. HIF pathway plays an important role in oxygen sensation of pulmonary hypertension. In previous study, we have found variations of EGLN1 gene which encoding prolyl-4 hydroxylase 2 (PHD2) in PPHN neonates. The present study is proposed to go on further confirmation of EGLN1 gene variations with larger sample size. Endothelial specific EGLN1 knockout mouse will be constructed and exposed to hypoxia. We will measure the right ventricular systolic pressure through catheterization of right ventricle and observe pathological change of pulmonary arteries. Gene expression, protein level in HIF pathway will be detected as well. This study will help to elucidate the mechanism of EGLN1 regulated HIF pathway in PPHN and provide new ideas for the manegement of PPHN.