支气管肺发育不良（BPD）并发肺高压（PH）是早产儿高病死率的重要原因，治疗棘手。Omega-3多不饱和脂肪酸（PUFAω-3）能通过血管内皮NO途径缓解PH。但目前尚无研究阐明PUFAω-3对BPD并发PH中肺血管内皮功能失调的影响及潜在机制。前期实验发现：PUFAω-3可改善BPD并发PH的肺血管重塑，下调肺血管发育密切相关miR-21的表达；还可降低致内皮功能障碍关键信号分子ADMA的水平；ADMA的代谢酶DDAH1被预测为miR-21靶标。我们推测PUFAω-3通过影响miR-21参与ADMA调控，从而改善BPD并发PH。本课题拟通过高氧诱导PH模型与原代内皮细胞培养技术，从整体、组织、细胞、分子水平阐明PUFAω-3对BPD并发PH中肺血管内皮的保护作用及诱导miR-21/DDAH1/ADMA信号的调控机制，可能为PUFAω-3对BPD并发PH的治疗提供理论基础和营养干预新策略。

Bronchopulmonary dysplasia (BPD) complicated by pulmonary hypertension (PH) is one of the most serious diseases and challenges of preterm infants. The prognosis of severe BPD complicated by PH is extremely poor, and current effective preventive measures or available therapies are still lacking. Omega-3 polyunsaturated fatty acids (PUFA ω-3) can improve PH via increased NO availability in endothelial cells. The effects and mechanisms of PUFA ω-3 on endothelial dysfunction in BPD complicated by PH has not been fully studied. In a pilot experiment, PUFA ω-3 supplementation was verified to prevent pulmonary vascular remodeling in hyperoxia-induced PH rat model and decrease the expression of microRNA-21 which has been shown to involved in both homeostasis and pathophysiology of pulmonary vascular development. Furthermore, our investigation suggested PUFA ω-3 reduced the level of ADMA, which is considered as an important signal of endothelial dysfunction. Based on computational algorithms, DDAH1, the metabolic enzyme of ADMA, has been predicted as a direct target of miR-21 and regulated by miR-21. Taken together, we speculate that the pathophysiologic intervention on BPD complicated by PH of miR-21 induced by PUFA ω-3 was related to the decreased levels of ADMA. However, the mechanisms by which PUFA ω-3 induced protective role on hyperoxia-induced endothelial dysfunction in PH remains unclear. Therefore, the present study aimed to evaluate the effects and investigate the mechanisms of PUFA ω-3 on the regulation of miR-21/DDAH1/ADMA signal pathway in pulmonary vascular endothelial cells and hyperoxia-induced rat model of PH, which strongly resembles BPD complicated by PH in preterm infants. Our findings may provide important theoretical basis and strategy for treatment by PUFA ω-3 on BPD complicated by PH in premature.