miR-200c介导Sirt1/Drp-1通路参与慢性间歇性缺氧诱导的视网膜微血管功能异常的机制研究

阻塞性睡眠呼吸暂停(OSA)与多种视网膜血管类疾病的进展恶化密切相关。本课题组前期研究发现OSA模型中慢性间歇性缺氧(CIH)可引起视网膜微血管内皮依赖性舒张功能障碍，并伴随视网膜组织中miR-200c的显著上调，而抑制miR-200c的表达可保护视网膜微血管受损的舒张功能。据此提出“miR-200c通过血管内皮细胞介导CIH导致的视网膜微血管功能异常”的假说。本研究拟用慢性间歇性缺氧动物和细胞模型，从组织-细胞-分子水平探究：(1)明确CIH诱导的miR-200c上调与视网膜微血管功能异常之间的关联；(2)miR-200c是否通过Sirt1/Drp-1通路介导CIH诱导的内皮细胞线粒体动力学异常，引起eNOS及NO下调，从而导致视网膜微血管功能异常。本研究可为慢性间歇性缺氧这一病理因素对视网膜血管损害提供新的认知，并为视网膜血管疾病的防治提供潜在的治疗靶点。

Obstructive sleep apnea(OSA)is closely related to the deterioration of various retinal vascular diseases. Our previous clinical study showed that in OSA animal model, chronic intermittent hypoxia(CIH), the most typical pathophysiological feature of OSA, could induce retinal microvascular dysfunction and the significant upregulation of miR-200c in the retina tissue, and inhibition of miR-200c could partly restore the dysfunction of retinal microvessels. Based on these, we proposed the hypothesis "miR-200c mediates retinal microvascular dysfunction induced by CIH with endothelial cells as its target". In this study, CIH animal and cell models were used to explore: (1)the possible relationship between the upregulation of miR-200c and the retinal microvascular dysfunction induced by CIH; (2) whether miR-200c mediates excessive mitochondrial fission in CIH through SIRT1/Drp-1 pathway, and causes the reduction of eNOS and NO and leads to the retinal microvascular dysfunction. This study might improve our knowledge of the damage of retinal microvasculature induced by CIH, and be helpful to explore potential therapeutic target in retinal vascular diseases.