补肾养血明目方基于线粒体途径对视网膜色素上皮细胞氧化应激损伤的保护作用研究

Retinal pigment epithelium plays important roles in maintaining the normal retinal structure and visual function. Mitochondrial dysfunction caused by oxidative stress and mediated RPE cell damage has close relationship with the development of age-related macular degeneration, the main pathogenesis is due to RPE apoptosis induced by structure and function anomalies of mitochondrial membrane and mitochondrial damage caused by reactive oxide species. Therefore, reducing the attack of ROS to mitochondrion, stabilizing membrane structure and potential of mitochondrion, decreasing mtDNA damage are the key ways to protect RPE from oxidative stress damage, and also the important targets for AMD prevention. Bu Shen Yang Xue Ming Mu Formula is an empirical formula commonly used in our clinics. This project is designed based on the primary clinical observation and experimental study. With the AMD mouse model induced by cigarette smoke-related Hydroquinone and in vitro RPE damage model induced by Hydroquinone as study objects, by means of modern research techniques like cellular and molecular microbiology approaches, pathology, electron microscopy, ocular electrophysiology, to thoroughly investigate the effect and its mechanism of Bu Shen Yang Xue Ming Mu Fang on protecting RPE from oxidative damage, thus to supply reliable and scientific evidence for clinical application.

视网膜色素上皮（RPE）细胞在维持正常眼底结构和视功能方面发挥着不可替代的作用。氧化应激导致的线粒体功能失调及其介导的RPE细胞损伤与年龄相关性黄斑变性（AMD）的发生发展密切相关，其主要的发病机制是活性氧自由基（ROS）导致线粒体膜结构和功能异常及线粒体DNA（mtDNA）损伤所引发的RPE细胞凋亡。因此，减少ROS对线粒体的攻击，稳定线粒体膜结构和膜电位、减少mtDNA的损伤是保护RPE细胞氧化应激损伤的关键途径，亦是防治AMD的重要靶点。补肾养血明目方是名老中医临床多年治疗AMD的经验方，本课题是在前期临床观察和实验研究的基础上，进一步以烟雾中主要化学成分氢醌诱导的小鼠AMD模型及氢醌诱导的体外RPE细胞损伤模型为研究载体，采用细胞分子生物学、病理学、电镜、眼电生理学等研究技术，深入探讨补肾活血明目方对RPE细胞氧化损伤的保护作用及作用机制，为临床治疗AMD提供科学依据。

视网膜色素上皮（RPE）细胞在维持正常眼底结构和视功能方面发挥着不可替代的作用。补肾养血明目方是名老中医临床多年治疗AMD的经验方，在前期研究的基础上，我们从动物实验和体外细胞培养两方面系统探讨了补肾养血明目方对视网膜色素上皮（RPE）细胞氧化损伤的保护作用。结果表明补肾养血明目方可减轻RPE-Bruch膜-脉络膜的损伤，减少沉积物的形成，减轻Bruch膜的增厚，降低视网膜细胞特别是RPE细胞的凋亡率，促进mtDNA修复以及提高外周血清SOD活性。体外实验表明早期预防性用药能更有效的保护ARPE-19细胞，降低凋亡率，增加线粒体代谢和mtDNA修复，提高细胞内SOD和GSH-PX活力。补肾养血明目方可从多靶点，特别是线粒体途径保护RPE细胞损伤，研究结果为临床治疗AMD提供了科学依据。