MiR-15b在糖尿病增殖性视网膜病变进展中的作用机制

糖尿病视网膜增殖性病变（PDR）是微血管过度形成造成的微血管病变，在云南地区高发。本课题组和前人研究发现：PDR血浆中VEGF显著高于单纯型（NPDR）和正常人群（NDR），而VEGF诱导血管内皮细胞增殖和成血管增加；PDR病人血浆和大鼠视网膜组织中，miR-15b表达下降；在内皮细胞中VEGF抑制miR-15b表达，而miR-15b抑制VEGF促增殖效应。miR-15b是否参与调控PDR未见报道。本项目在前期发现的基础上，在细胞和分子层次，结合动物模型实验，集中探讨：1.VEGF及其信号通路对于miR-15b表达调控作用。2.miR-15b抑制血管内皮细胞增殖和成血管的机制。3.在体动物模型研究miR-15b与PDR发生和发展之间的关联及机制。研究结果有望揭示miR-15b在PDR发生和发展过程中分子调控机制，为将来在体干预糖尿病视网膜病变提供理论依据和潜在靶点。

Proliferation diabetic retinopathy (PDR) is one of the most serious microvascular diseases derived from excessive microvessel formation. Currently, PDR has a high morbidity in Yunnan Province. We and others have showed that plasma vascular endothelial growth factor (VEGF) in PDR patients was significantly higher than that of non-proliferation diabetic retinopathy (NPDR) patients and normal controls(NDR).VEGF induced proliferation of vascular endothelial cells and formation of new blood vessels (angiogenesis). We also found the expression of miR-15b was decreased in plasma of diabetic patients and in retina of diabetic rats. VEGF could inhabit miR-15b expression,which further inhibit the proliferation of endothelial cells induced by VEGF. Hitherto, there is no study to characterize the exact role of miR-15b in the development of PDR. In this study, we performed experiments at both molecular and cellular levels, as well as using in vivo animal models to examine: 1. VEGF and its signal transduction in regulation of miR-15b expression; 2. mechanism of miR-15b inhibition for proliferation of vascular endothelial cells and angiogenesis; 3. the role of miR-15b in the development of PDR in animal model. Our results will reveal the molecular and cellular mechanism of miR-15b in PDR and provide helpful information regarding the therapy of PDR in the future.