肺血管结构重建和血管稳态失衡是肺动脉高压的主要特征，自噬与其关系近来备受关注。本团队前期研究发现，低氧使肺动脉平滑肌细胞（PASMC）增殖、自噬代偿性升高，抑制PI3K/AKT/mTOR可促进PASMC自噬性死亡。据报道lncRNA MALAT1、miR-503表达在肺动脉高压时出现变化，MALAT1作为ceRNA可下调miR-503表达，miR-503可抑制PI3K表达，故推测MALAT1/miR-503调控PI3K介导的自噬途径。故本项目拟研究MALAT1/miR-503相关自噬途径与低氧性肺动脉高压的关系，为其诊治寻求新靶点。本团队还发现双氢青蒿素（DHA）可抑制低氧性肺动脉高压并促进自噬，且抑制MALAT1表达。有报道DHA可抑制胶质瘤细胞PI3K表达，故本项目进一步探讨DHA对PI3K介导的PASMC自噬的影响以及MALAT1/miR-503的调控作用，为其临床应用提供实验依据。

Pulmonary hypertension can be manifested as pulmonary vascular structural remodeling and vascular homeostasis. There is a growing interest in relationship between autophagy and pulmonary hypertension. Our previous research has indicated that the proliferation of pulmonary artery smooth muscle cells (PASMC) could be promoted and autophagy could compensatively increase under hypoxia. Simultaneously, our data demonstrated that inhabitation of PI3K/AKT/mTOR signal pathway can promote autophagic death of PASMC. In study of pulmonary fibrosis, the expression of lncRNA MALAT1 and miR-503 changes in pulmonary hypertension. Moreover, the MALAT1 was reported as a ceRNA to competitively decrease the expression of miR-503, and miR-503 may inhibit the expression of PI3K. Based on studies above mentioned and data of our previous research ,we speculate that MALAT1/miR-503 may regulate PI3K-mediated autophagy pathway. Aiming to find a new target of pulmonary hypertension treatment, this project intends to explore the relationship between MALAT1/miR-503 related autophagy pathway and pulmonary hypertension caused by hypoxia. In addition, our prophase study has found that dihydroartemisinin (DHA) could decrease hypoxic-induced pulmonary hypertension in rats and activate autophagy. Under hypoxia, DHA can inhibit the expression of MALAT1 in lung tissue. Besides,it has been reported that DHA can inhibit the expression of PI3K in glioma cells . Therefore, this project aims to further investigate the role of DHA on PI3K-mediated autophagy pathway in PASMC, and to confirm the function of MALAT1/miR-503 in this pathophysiological process. This study will be helpful in providing more explicit evidence to support its widespread use of prevention and treatment of pulmonary hypertension.