石斛夜光丸调控Gq-GPCR/PLC/氧化应激通路干预视网膜光损伤的效应机制研究

项目名称： 石斛夜光丸调控Gq-GPCR/PLC/氧化应激通路干预视网膜光损伤的效应机制研究

项目编号： No.81473732

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 陈瑜

作者单位： 上海中医药大学

项目金额： 70万元

中文摘要： 光感受器细胞死亡及色素上皮细胞变性是多种视网膜退行性病变的共同病理环节，包括年龄相关性黄斑变性、视网膜色素变性等。视网膜光损伤病理表现与上述退行性病变一致，同时也是这些疾病的发病机制之一。因此，针对光损伤光感受器细胞死亡和色素上皮细胞变性的有效干预对多种视网膜退行性病变的治疗研究有着积极的理论和临床指导意义。石斛夜光丸是临床治疗视网膜退行性病变的经典有效方剂，然而其效应机制研究存在大量空白。申请人前期工作提示Gq-GPCR/PLC/氧化应激通路是光感受器细胞及色素上皮细胞病理改变的关键调控机制。本项目将以光感受器及色素上皮细胞为效应靶点，对石斛夜光丸及其补肾明目、清肝明目拆方的视网膜保护作用进行比较研究，并深入探讨各中药组方对Gq-GPCR/PLC/氧化应激信号级联反应的影响, 明确其各自明目效应的细胞靶点及分子效应环节，为其在视网膜退行性病变治疗中的应用提供科学的理论和实验依据。

中文关键词： 视网膜；中医药；分子机制；石斛夜光丸；光损伤

英文摘要： Death and degeneration of retinal pigment epithelial cells is the central mechanism underling the pathogenesis of a variety of retinal degenerative disorders, including age-related macular degeneration (AMD) and retinitis pigmentosa. Light-induced retinopathy not only shares the similar pathological changes with these retinal degenerative disorders in terms of photoreceptor cell death and RPE degeneration, it is also mechanistically implicated in the etiology of these disorders. Therefore, research aiming at effective intervention of light-induced retinopathy will offer theoretical and practical insight into the clinical management of AMD and related retinal degenerative disorders. Using AMD as an example, effective therapeutic measures are still lacking as a result of unclarified mechanisms in its pathogenesis. ShiHuYeGuangWan (SHYGW) has long been clinically applied in the treatment of AMD and other retinal degenerative disorders. Although AHYGW is recognized as therapeutically effective, the mechanisms underlining its therapeutic effects remain to be explored. Our previous studies have uncovered that light-induced retinopathy is mechanistically caused by altered functionality Gq-GPCR and NADPH oxidase-mediated ROS overproduction. Enhanced functionality of Gq-GPCR, increased PLC activity and NADPH oxidase-mediated ROS production forms a novel signaling cascade contributing to the photoreceptor cell death during light-induced retinopathy. Therefore, our current study propose to evaluate and compare the protective effects of SHYGW and major formula derived from SHYGW, namely BuShen and QinGan composition, on photoreceptor cells and RPE. Further mechanistic studies will be focused on elucidating the impact of each of herbal formulation on Gq-GPCR/PLC/NADPH oxidase/ROS. In the end, we aim to delineate the cellular target and molecular element that mediate the effect of SHYGW, which will ultimately provide scientific and experimental evidence supporting the clinical application of SHYGW in the treatment of retinal degenerative disorders.

英文关键词： Retina;Traditional Chinese Medicine;Molecular mechanism;ShiHuYeGuangWan;Light-induced damage