College of Food Engineering and Nutritional Science, Shaanxi Normal University, Xi'an 710119, China.
Tianjin Key Lab of Ophthalmology and Visual Science, Tianjin Eye Hospital, Tianjin Eye Institute, Tianjin 300384, China.
Nutr Res. 2024 Feb;122:55-67. doi: 10.1016/j.nutres.2023.12.003. Epub 2023 Dec 15.
Hyperglycemia-related retinopathy is a disease with a high blindness rate. Recent reports indicate that many flavonol compounds have the potential to prevent the occurrence of disease in the retina by regulating the gut-retina axis. Here, we hypothesized that quercetin could alleviate the symptoms of retinopathy. To clarify the mechanism, Sprague Dawley rats were fed a high-fat diet containing quercetin for 12 weeks and injected with streptozotocin in the ninth week. Additionally, neomycin and ampicillin were used to establish a pseudo-sterile rat model. Afterward, changes in the retina were investigated by using electroretinogram and optical coherence tomography. Blood and tissue samples were collected and biochemical components were analyzed. The extent of intestinal injury was determined via hematoxylin-eosin staining. Microbial community structure was analyzed by using 16S ribosomal RNA sequencing. Finally, the expression of genes was analyzed using real-time polymerase chain reaction. The results showed that quercetin reduced the decline in electroretinography amplitude and outer nuclear layer thickness, increased the activities of antioxidant enzymes, decreased the contents of proinflammatory factors and blood glucose, enhanced the concentration of insulin, and inhibited intestinal dysbiosis and improved gut morphology. Importantly, the underexpression of nuclear factor erythroid-2 related factor 2 in the retina was reversed by quercetin. However, trend changes were no longer significant in most of the indicators after antibiotic treatment. In summary, quercetin has therapeutic effects on retinopathy by regulating the gut-retina axis and nuclear factor erythroid-2 related factor 2 pathway, and the presence of gut microbiota helps quercetin exert its effects on the retina.
高血糖相关的视网膜病变是一种致盲率较高的疾病。最近的报告表明，许多类黄酮化合物有可能通过调节肠道-视网膜轴来预防视网膜疾病的发生。在这里，我们假设槲皮素可以缓解视网膜病变的症状。为了阐明其机制，将 Sprague Dawley 大鼠用含有槲皮素的高脂肪饮食喂养 12 周，并在第 9 周注射链脲佐菌素。此外，使用新霉素和氨苄青霉素建立假无菌大鼠模型。之后，通过视网膜电图和光相干断层扫描来研究视网膜的变化。采集血液和组织样本并分析生化成分。通过苏木精-伊红染色来确定肠道损伤的程度。通过 16S 核糖体 RNA 测序来分析微生物群落结构。最后，使用实时聚合酶链反应分析基因的表达。结果表明，槲皮素减少了视网膜电图幅度和外核层厚度的下降，增加了抗氧化酶的活性，降低了促炎因子和血糖的含量，提高了胰岛素的浓度，抑制了肠道失调，改善了肠道形态。重要的是，槲皮素逆转了核因子红细胞 2 相关因子 2 在视网膜中的低表达。然而，在抗生素治疗后，大多数指标的趋势变化不再显著。总之，槲皮素通过调节肠道-视网膜轴和核因子红细胞 2 相关因子 2 途径对视网膜病变具有治疗作用，肠道微生物群有助于槲皮素发挥其对视网膜的作用。
