NADPH氧化酶通路和mitoKATP介导莱菔硫烷对糖尿病大鼠视网膜神经节细胞的保护作用

Diabetic retinopathy (DR) is classically thought of as a microvascular disease of the retinal capillaries. Studies have shown that diabetes also impairs retinal neuronal function before the onset of visible vascular lesions. Recent studies suggest that oxidative stress plays a major role on retinal neuronal dysfunction in diabetes. Sulforaphane (SF), which can be obtained in cruciferous vegetables such as broccoli, exerts protective effects in response to oxidative stress in various tissues. We studied retinal neurocircuitry of db/db mice and observed impaired visual function during the early stage of DR. Application of various antioxidants protected retinal ganglion cells (RGCs). Accordingly, this research project will have a comprehensive study of the role of SF in protection of RGCs in induced diabetic rats at the molecular, cellular and integrative level. The role of NADPH oxidase signaling pathway and retinal mitoKATP in the neuroprotective effects of SF on RGCs of diabetic rats will be investigated therewith. Furthermore, the antioxidation of SF in protection of retinal structure and function will be further explored. The research results will not only help to clarify the neuroprotective effects of SF on the visual function in diabetic rats, but provide new strategy for prevention and treatment of DR.

糖尿病视网膜病变（DR）中视网膜神经细胞的功能损伤发生在临床可见的血管损伤之前，而且是导致糖尿病视觉丧失的直接因素。氧化应激是引起糖尿病视网膜神经节细胞（RGCs）功能损伤的主要因素之一。莱菔硫烷（SF）广泛存在于十字花科蔬菜中，特别是西兰花，研究表明SF在多种组织的氧化应激反应中发挥保护效应。我们过去的研究发现db/db小鼠视网膜神经通路在疾病初期就出现功能异常，而抗氧化剂可使RGCs受到不同程度的保护。本项目将深化前期研究，从分子、细胞和系统水平综合研究SF对糖尿病大鼠RGCs的保护效应，探讨NADPH氧化酶通路和线粒体ATP敏感钾通道（mitoKATP）在SF保护糖尿病视网膜RGCs中的作用，并进一步在细胞水平探讨SF对糖尿病大鼠RGCs视觉功能的保护作用。研究结果不仅有助于阐明SF对DR视觉功能的神经保护作用机制，而且为临床上早期防治DR提供了新的思路。