Department of Ophthalmology, Qinghai Red Cross Hospital, Xining, Qinghai, China.
Int J Med Sci. 2017 Aug 17;14(10):943-950. doi: 10.7150/ijms.19391. eCollection 2017.
High-altitude retinopathy represents retinal functional changes associated with environmental challenges imposed by hypobaric hypoxia, but the detailed cellular and molecular mechanism underlying this process remains unclear. Our current investigation was to explore the effect of hypobaric hypoxia on the rat retina and determine whether resveratrol has a protective efficacy on the hypoxic damage to the retina. Experiment rats were randomly grouped as the control group, hypoxia group and resveratrol intervention group. The hypoxia group and the resveratrol intervention group were maintained in a low-pressure oxygen cabin, and the resveratrol intervention group was given daily intraperitoneal injections with resveratrol. We found that hypobaric hypoxia increased thioredoxin 1 (Trx1) and thioredoxin 2 (Trx2) expression in retinas, and resveratrol treatment significantly reversed these changes ( < 0.05, < 0.05 respectively). In comparison with controls, hypoxia upregulated the mRNA expression levels of caspase3 ( < 0.001), caspase9 ( < 0.01), heat shock protein 70 (Hsp70) ( < 0.05), heat shock protein 90 (Hsp90) ( < 0.001) and hypoxia-inducible factor-1 (HIF-1) ( < 0.05). Resveratrol administration caused a significant decrease in the gene expression of caspase3 (< 0.001), HSP90 ( < 0.05) and HIF-1 mRNA ( < 0.01) as well as an increase in HSP70 mRNA when compared with the hypoxia group. These findings indicated that resveratrol exerted an anti-oxidative role by modulating hypoxia stress- associated genes and an anti-apoptosis role by regulating apoptosis-related cytokines. In conclusion, hypobaric hypoxia may have a pathological impact on rat retinas. The intervention of resveratrol reverses the effect induced by hypobaric hypoxia and elicits a protective response to the stress.
高原视网膜病变代表了与低压缺氧引起的环境挑战相关的视网膜功能变化,但这一过程的详细细胞和分子机制仍不清楚。我们目前的研究旨在探讨低压缺氧对大鼠视网膜的影响,并确定白藜芦醇是否对缺氧对视网膜的损伤具有保护作用。实验大鼠随机分为对照组、缺氧组和白藜芦醇干预组。缺氧组和白藜芦醇干预组在低压氧舱中维持,白藜芦醇干预组每天给予腹腔注射白藜芦醇。我们发现,低压缺氧增加了视网膜中硫氧还蛋白 1(Trx1)和硫氧还蛋白 2(Trx2)的表达,而白藜芦醇处理显著逆转了这些变化(分别为 < 0.05, < 0.05)。与对照组相比,缺氧上调了 caspase3( < 0.001)、caspase9( < 0.01)、热休克蛋白 70(Hsp70)( < 0.05)、热休克蛋白 90(Hsp90)( < 0.001)和缺氧诱导因子 1(HIF-1)( < 0.05)的 mRNA 表达水平。与缺氧组相比,白藜芦醇给药导致 caspase3(< 0.001)、HSP90( < 0.05)和 HIF-1 mRNA 表达显著降低,HSP70 mRNA 表达增加。这些发现表明,白藜芦醇通过调节与缺氧应激相关的基因发挥抗氧化作用,并通过调节凋亡相关细胞因子发挥抗凋亡作用。总之,低压缺氧可能对大鼠视网膜产生病理影响。白藜芦醇的干预逆转了低压缺氧引起的效应,并对应激产生了保护反应。