白藜芦醇防护糖尿病早期视网膜病变的作用及分子机制

项目名称： 白藜芦醇防护糖尿病早期视网膜病变的作用及分子机制

项目编号： No.81202206

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 预防医学、地方病学、职业病学、放射医学

项目作者： 曾凯宏

作者单位： 电子科技大学

项目金额： 23万元

中文摘要： 糖尿病视网膜病变（DR）是世界范围内致盲的主要原因之一。申请人前期研究表明，视网膜muller细胞（RMCs）损伤发生在DR早期。探讨DR RMCs损伤的膳食防护具有重要意义。白藜芦醇（Res）作为天然植物多酚，其对DR的防护作用已被证实，但Res对RMCs损伤的作用及分子机制尚不清楚。微小RNAs（miRNAs）是新近发现的DR防治靶点，某些miRNAs可能在Res防护DR中发挥作用。本项目基于前期研究，采用STZ诱导SD大鼠动物模型，重点探讨Res对DR RMCs损伤的影响及其与miR-29b/RAX/PKR/NF-κB的关系；并结合体外高糖培养RMCs，运用特异性抑制剂、siRNA、荧光定量PCR等技术，深入研究Res通过影响miR-29b调节NF-κB凋亡通路防护DR早期RMCs损伤的分子机制。本研究旨在深入揭示Res防护DR早期病变的分子机制，为指导人们早期防治DR提供科学依据。

中文关键词： 糖尿病视网膜病变；白藜芦醇；微小RNA29b；视网膜Muller细胞；凋亡

英文摘要： Diabetic retinopathy (DR) is one of the leading causes of blindness worldwide. Although significant progress has been made, there is still no efficient treatment of this disease. One of the reasons may be that our knowledge of the mechanisms underlying early pathogenic processes is lacking. Our previous studies have indicated that structural and Functional damage to the retinal muller cells (RMCs) occur prior to the onset of vasculature abnormalities and ultimately lead to vascular disease. Therefore, it is crucial to find additional treatments that prevent or slow the damage of RMCs in DR. Resveratrol (Res) is a dietary polyphenol derived from grapes, peanuts, and other plant sources. Res has been shown to prevent DR in several studies. However, the protective effects of Res on RMCs' injury and its molecular mechanisms are not understood. MicroRNAs (miRNAs) are endogeneous small RNAs (less than 25 nt) that play key regulatory roles targeting mRNA for specific cleavage, mRNA deadenylation and decay, translational repression or activation. Recently, increasing evidence has indicated that miRNAs play important roles in DR. Some of these miRNAs may be the targets of Res anti-DR. In this project, we address the possible effects and underlying molecular mechanisms of Res on RMCs' damage in early phase of DR. In vivo,

英文关键词： diabetic retinopathy；resveratrol；microRNA-29b；retinal Muller cells；apoptosis