Department of Histology and Embryology, Taishan Medical University, Taian 271000, Shandong, China.
Exp Eye Res. 2012 Jan;94(1):117-27. doi: 10.1016/j.exer.2011.11.016. Epub 2011 Dec 3.
Molecular hydrogen (H(2)) is an efficient antioxidant that can selectively reduce hydroxyl radicals and inhibit oxidative stress-induced injuries. We investigated the protective effects and mechanism of hydrogen-rich saline in a glutamate-induced retinal injury model. Retinal excitotoxicity was induced in healthy guinea pigs by injecting glutamate into the vitreous cavity. After 30 min, hydrogen-rich saline was injected into the vitreous cavity, the peritoneal cavity or both. Seven days later, the retinal stress response was evaluated by examining the stress biomarkers, inducible nitric-oxide synthase (iNOS) and glucose-regulated protein 78 (GRP78). The impaired glutamate uptake was assessed by the expression of the excitatory amino acid transporter 1(EAAT-1). The retinal histopathological changes were investigated, focusing on the thicknesses of the entire retina and its inner layer, the number of cells in the retinal ganglion cell layer (GCL) and the ultrastructure of the retinal ganglion cells (RGCs) and glial cells. Compared with the glutamate-induced injury group, the hydrogen-rich saline treatment reduced the loss of cells in the GCL and thinning of the retina and attenuated cellular morphological damage. These improvements were greatest in animals that received H(2) injections into both the vitreous and the peritoneal cavities. The hydrogen-rich saline also inhibited the expression of glial fibrillary acidic protein (GFAP) in Müller cells, CD11b in microglia, and iNOS and GRP78 in glial cells. Moreover, the hydrogen-rich saline increased the expression of EAAT-1. In conclusion, the administration of hydrogen-rich saline through the intravitreal or/and intraperitoneal routes could reduce the retinal excitotoxic injury and promote retinal recovery. This result likely occurs by inhibiting the activation of glial cells, decreasing the production of the iNOS and GRP78 and promoting glutamate clearance.
分子氢（H2）是一种有效的抗氧化剂，可选择性还原羟自由基并抑制氧化应激诱导的损伤。我们研究了富氢生理盐水在谷氨酸诱导的视网膜损伤模型中的保护作用和机制。通过向玻璃体腔注射谷氨酸诱导健康豚鼠视网膜兴奋性毒性。30 分钟后，将富氢生理盐水注入玻璃体腔、腹腔或两者。7 天后，通过检测应激生物标志物诱导型一氧化氮合酶（iNOS）和葡萄糖调节蛋白 78（GRP78）评估视网膜应激反应。通过兴奋性氨基酸转运体 1（EAAT-1）的表达评估谷氨酸摄取受损情况。研究了视网膜组织病理学变化，重点关注整个视网膜及其内层的厚度、视网膜神经节细胞层（GCL）中的细胞数量以及视网膜神经节细胞（RGCs）和神经胶质细胞的超微结构。与谷氨酸诱导损伤组相比，富氢生理盐水治疗减轻了 GCL 细胞丢失和视网膜变薄，并减轻了细胞形态损伤。在玻璃体和腹腔均接受 H2 注射的动物中，这些改善最为明显。富氢生理盐水还抑制了胶质细胞中 GFAP 的表达、小胶质细胞中的 CD11b 以及神经胶质细胞中的 iNOS 和 GRP78。此外，富氢生理盐水增加了 EAAT-1 的表达。总之，通过玻璃体内或/和腹腔内途径给予富氢生理盐水可减轻视网膜兴奋性毒性损伤并促进视网膜恢复。这一结果可能是通过抑制神经胶质细胞的激活、减少 iNOS 和 GRP78 的产生以及促进谷氨酸清除来实现的。
