肺动脉平滑肌细胞（PASMCs）增殖是缺氧肺动脉高压的最显著特征，其机制不清楚是导致临床上该疾病药物疗效不佳的最主要原因。长链非编码RNA（lncRNA）在心血管疾病研究中取得了重要进展，但lncRNA在缺氧肺动脉高压中的作用及机制仍不清楚。前期结果显示缺氧肺动脉高压小鼠肺动脉中lncRNA 母系表达基因3（MEG3）和pim-1表达升高，而miR-328表达下降；生物信息学软件预测出MEG3与miR-328，miR-328与pim-1具有结合可能性。因此本课题假设“缺氧诱导MEG3表达升高，MEG3负向调控miR-328，使miR-328调控pim-1表达的能力降低，从而引起PASMCs增殖、肺血管重构”。本课题拟采用微量热泳动技术、脂质体肺靶向给药等技术证实上述实验假设，确定lncRNA MEG3在缺氧PASMCs增殖中的作用，为临床防治肺动脉高压提供新思路。

The proliferation of pulmonary artery smooth muscle cells (PASMCs) is the most significant feature of hypoxic pulmonary hypertension, however, the exactly mechanism for PASMCs proliferation remains unclear leads to the less therapy efficiency of current drugs for pulmonary hypertension. The roles of long non-coding RNA (lncRNA) in cardiovascular diseases have made a great progress, whereas lncRNA contributes hypoxic pulmonary hypertension and the underling mechanism still unknown. Our previous results have demonstrated that the expression of lncRNA maternally expressed gene 3 (MEG3) and pim-1 were increased, whereas microRNA-328 (miR-328) expression was decreased in pulmonary arterials from hypoxic pulmonary hypertension mice. According to the Target Scan software prediction, there is complementary base between lncRNA-MEG3 and miR-328, miR-328 and the mRNA of pim-1. These results lead us to hypothesis that “hypoxia increases the expression of lncRNA-MEG3, lncRNA-MEG3 targets to miR-328 and inhibits miR-328 expression, the down-regulation of miR-328 leads to the enhanced expression of pim-1, which contributes to PASMCs proliferation, finally leading to pulmonary vascular remodeling”. This study will employ microscale thermophoresis, liposome lung targeting drug delivery and other molecular biology technical to confirm our hypothesis. The results of this study will determine the role of lncRNA MEG3 in hypoxic PASMCs proliferation, and provide new clinical prevention and treatment schemes for pulmonary arterial hypertension.