lncRNA-MALAT1作为ceRNA参与miR-218调控慢性间歇低氧诱导内皮细胞凋亡的作用机制

阻塞性睡眠呼吸暂停低通气综合征（OSAHS）是一种导致多系统多器官损伤的睡眠障碍性疾病，慢性间歇低氧(CIH)是其相关并发症的病理生理基础。我们前期研究发现，miR-218在CIH内皮细胞中表达上调，阻遏miR-218表达可通过抑制Robo1的激活而显著降低缺氧诱导因子-1α（HIF-1α）的表达，减轻CIH下的主动脉内皮细胞凋亡。本项目在此基础上结合最新的国际研究前沿进展，将ceRNA机制引入miR-218调控CIH内皮细胞损伤中，结合生物信息学预测及与miR-218存在互作关系的lncRNA，探讨发挥ceRNA功能的lncRNA与miR-218之间的调控关系及lncRNA调控CIH内皮损伤的作用及机制，同时分析编码lncRNA基因甲基化对lncRNA-MALAT1表达及内皮细胞凋亡的影响，为OSAHS相关心血管损伤的发生发展机制、诊断分子标志物的筛选以及临床治疗提供理论基础和实验依据。

Obstructive Sleep Apnea-Hypopnea Syndrome (OSAHS) is a sleep disorder that causes multiple system organ damage. Chronic intermittent hypoxemia (CIH) is a pathophysiological basis of its associated complications. In our previous study, miR-218 was found to be upregulated in CIH endothelial cells, and knockdown of miR-218 expression significantly reduced the expression of HIF-1α (HIF-1α) and the induction of CIH by inhibiting the activation of Robo1 Aortic endothelial cell apoptosis. Based on our previous study and combined the latest advances in international research, we involve the ceRNA mechanism into CIH-induced endothelial injury which is regulated by miR-218. Combined with the bioinformatics which predicted the interactions between miR-218 and lncRNA, we intend to explore the relationship between lncRNA which has the function of ceRNA and miR-218, and to find the role of lncRNA in CIH-induced endothelial injury and its mechanism. Meanwhile, the effects of methylation of lncRNA encoding gene on the expression of lncRNA-MALAT1 and endothelial cell apoptosis will also be analyzed.These will provide theoretical and experimental basis for verifying the mechanism of OSAHS-related cardiovascular injury and identifying biomarker for the early diagnosis and prognosis in OSAHS-related cardiovascular injury.