双靶点干预对糖尿病视网膜病变中“血管-纤维化开关”的调控

项目名称： 双靶点干预对糖尿病视网膜病变中“血管-纤维化开关”的调控

项目编号： No.81460089

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 胡博杰

作者单位： 和田地区人民医院

项目金额： 47万元

中文摘要： 增殖性糖尿病视网膜病变（PDR）的治疗中，如何在抑制新生血管的同时减少纤维血管膜的形成，备受关注。血管新生和纤维化增殖之间存在转换机制，称为血管-纤维化开关。我们前期工作中证实可以通过促纤维化因子（CTGF）与促血管生成的因子（VEGF）的比值（CTGF/VEGF）将血管-纤维化开关数值化。在此基础上，本课题拟选用临床最为有效的VEGF拮抗剂lucentis和CTGF拮抗剂CTGF shRNA进行双靶点干预；通过动物实验，检测视网膜电生理、血管结构、血-视网膜屏障等及CTGF、VEGF表达水平的改变；通过细胞实验，检测视网膜血管内皮细胞和脉络膜成纤维细胞中CTGF、VEGF表达变化、细胞增殖及收缩力的改变；并对涉及的Wnt/β-catenin信号通路中相互调节机制进一步探讨。我们期望该干预策略为阻断PDR的新生血管和纤维增殖病变的进展，提供一个新的思路。

中文关键词： 双靶点干预；糖尿病视网膜病变；基因表达调控；血管-纤维化开关

英文摘要： In the treatment of Proliferative diabetic retinopathy (PDR), it is concerned how to inhibite neovascularization and reduce the formation of fibrous membranes meanwhile. The conversion mechanism between angiogenesis and fibrosis proliferation is called vascular - fibrosis switch. Our previous work demonstrated that changing the ratio of pro-fibrotic factor (CTGF) and pro-angiogenic factor (VEGF) (CTGF / VEGF) can contral the vascular - fibrosis switch. On this basis, this paper choose the most effective antagonists of VEGF named lucentis in clinic and antagonists of CTGF named CTGF shRNA to interven double targets; through animal experiments, detect retinal electrophysiology, vascular structures, blood - retinal barrier, and expression levels of CTGF and VEGF; through cell experiments, detect expression levels of CTGF and VEGF in retinal vascular endothelial cells and choroidal fibroblasts, cell proliferation and contraction force; and discuss the adjustment mechanism about Wnt / β-catenin signaling pathway. We expect the intervention strategies can provide a new way to block the progress of the neovascularization and proliferation of PDR.

英文关键词： Dual-target intervention;diabetic retinopathy;regulation of gene expression;angio-fibrotic switch