中文摘要
糖尿病视网膜病是成人致盲的首要原因,现有药物对部分患者无效。复方血栓通治疗糖尿病视网膜病疗效显著,但其药理机制与物质基础不明,不利于其临床广泛使用。我们已经证实复方血栓通不但可以抑制血管内皮生长因子在大鼠视网膜组织中的表达,而且影响该生长因子上游Hippo通路蛋白的活性;我们进一步应用分子对接技术筛选了复方血栓通调控Hippo通路的可能的活性成分。后期我们将在视网膜血管内皮细胞中,过表达或敲除Hippo通路核心基因,观察复方血栓通对细胞增殖、迁移、血管形成等指标的影响,揭示基于Hippo通路的复方血栓通的药理机制;然后运用高内涵系统分析复方血栓通可能的活性成分(组合)对细胞功能及Hippo通路活性的影响,最终通过检测糖尿病动物病理指标的变化,确认复方血栓通治疗糖尿病视网膜病的物质基础。本课题不仅为研究中药复方的药理机制及物质基础提供新的研究模式,而且为防治糖尿病视网膜病提供新的靶标。
英文摘要
Diabetic retinopathy is one of the most prominent complications of diabetes and the effect of anti-vascular endothelial growth factor drug is limited. FufangXueshuantong has been described for its medicinal effect against diabetic retinopathy, but the underlying mechanism and active substance have not been clarified. Hippo pathway is reported to regulate vascular endothelial growth factor. In previous results, we showed that FufangXueshuantong inhibited vascular pathological changes, suppressed vascular endothelial growth factor expression and improved activity or content of Hippo pathway. Furthermore, we discovered the potential substances using Hippo structure based virtual screening..The purpose of present study is to evaluate if Hippo pathway plays key roles in the medical effect of FufangXueshuantong, calculate and verify the bioactive molecules from FufangXueshuantong when Hippo pathway is perceived as targets. In the following study, we will measure the cell viability, cell migration and tube formation of retinal vascular endothelial cells after the Hippo pathway has been overexpressed or inhibited. And then we can analyze the role of the Hippo pathway in the therapeutic effect of FufangXueshuantong. Moreover, we will examine the cell function of retinal vascular endothelial cells using high content screening, then investigate the changes of retinal vascular morphology in diabetic mice after FufangXueshuantong is administered. In the end, we can determine the active substances of FufangXueshuantong by combining the efficacy and the Hippo changes. This project will contribute to reveal a new regulator for diabetic retinopathy, provide a new mode to elucidate the mechanism and active substrate for Chinese medicine and at last lay a foundation for development of FufangXueshuantong.
