金丝桃苷对糖尿病视网膜病变保护作用的分子机制研究

Diabetic retinopathy (DR) is one of the most common microvascular complications of Diabetes, high glucose-induced retinal vascular endothelial injury is the initiating factor of DR's occurrence。Recently, many studies have shown that, non-enzymatic glycosylation generated terminal glycation products and increased polyol pathway have played key roles to the apoptosis of DR vascular endothelial cells. In the pre-trial, our group has found that hyperin can play a protective effect on high glucose-induced retinal vascular endathelial cells injury in rats，at the same time, it can also increase the activity of SOD and reduce the generation of MDA。In order to explore the mechanism of the action of the hyperin furtherly, we are ready to adopt the diabetic retinopathy model in the subject，to observe the influence of the hyperin on the DR retinal vascular endothelial cells, and the role of it to the formation of glycosylation product and the pathway of polyol, for that we can fond the role of target from clearence of the oxygen free radicals, reduction of the generation of alcohol and acetone terminal glycosylationproducts, inhibition of activity, of aldose reductase etc. ，and reveal the mechanism of the production from Hyperin to the DR. Thus, we can provide theoretical and experimental basis for the development and application of the hyperin.

糖尿病视网膜病变（DR）是糖尿病最常见的微血管并发症之一，高糖诱导的视网膜血管内皮损伤是DR发生的始动因素。目前许多研究表明非酶糖基化生成的终末糖基化产物和多元醇信号通路增加对DR血管内皮细胞凋亡起关键作用。在前期试验中，本课题组发现金丝桃苷对高糖诱导的大鼠视网膜血管内皮细胞损伤有保护作用，同时能提高SOD活力并减少MDA生成。为进一步探讨金丝桃苷的作用机制，本课题拟采用糖尿病视网膜病变模型，观察金丝桃苷对DR视网膜血管内皮细胞凋亡的影响；研究金丝桃苷对终末糖基化产物生成和多元醇信号通路的作用，从清除氧自由基、减少丙酮醛与终末糖基化产物生成、抑制醛糖还原酶活性等方面寻找作用靶点，从细胞及分子层面揭示金丝桃苷对DR视网膜血管内皮细胞的保护机制，为金丝桃苷的开发和应用提供理论及实验依据。