Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100193, China; Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, China; Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, China.
Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100193, China; Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, China; Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine, Ministry of Education, China.
Eur J Pharmacol. 2021 Mar 15;895:173893. doi: 10.1016/j.ejphar.2021.173893. Epub 2021 Jan 22.
Diabetic retinopathy (DR) is a widespread vision-threatening disease in working people. Müller cells are important glial cells that participate in the blood retinal barrier and promote the maintenance of retinal physiological and structural homeostasis. Müller cell apoptosis and autophagy play an important role in the pathogenesis of DR. Gypenoside XVII (Gyp-17) exerts strong antiapoptotic and autophagic activities. However, the effect of Gyp-17 on DR and its mechanism of action have not been elucidated. This study explored the effect of Gyp-17 on early DR and Müller cell injury in db/db mice. Blood glucose and blood lipids were measured. Optical coherence tomography and fundus fluorescein angiography were applied to detect retinal thickness and vascular leakage, respectively. Hematoxylin eosin staining assessed the pathological changes of the retina. Retinal oxidative environment and cell apoptosis and autophagy were monitored using commercial kits, immunofluorescence, and Western blot assays. Results showed that Gyp-17 exerted no significant effect on blood glucose and lipid levels but maintained normal retinal permeability, physiological structure, high anti-oxidative enzyme expression, and the thickness of the inner nuclear layer compared with the model group. Moreover, Western blot analysis and TUNEL assay indicated that Gyp-17 significantly decreased pro-apoptotic-related protein expression and increased pro-autophagy-related protein expression compared with the model group. Immunofluorescence colocalization exhibited that the regulating action of Gyp-17 may focus on Müller cells. These data strongly demonstrate that Gyp-17 prevents early DR by decreasing apoptosis and increasing autophagy in Müller cells. Gyp-17 may be a candidate drug for early DR therapy.
糖尿病性视网膜病变（DR）是一种常见的工作人群致盲性眼病。Müller 细胞是重要的神经胶质细胞，参与血视网膜屏障的形成，并促进视网膜生理和结构的稳态维持。Müller 细胞凋亡和自噬在 DR 的发病机制中发挥重要作用。绞股蓝皂苷 XVII（Gyp-17）具有很强的抗凋亡和自噬活性。然而，Gyp-17 对 DR 的作用及其作用机制尚未阐明。本研究探讨了 Gyp-17 对 db/db 小鼠早期 DR 和 Müller 细胞损伤的影响。测量血糖和血脂。应用光学相干断层扫描和眼底荧光血管造影分别检测视网膜厚度和血管渗漏。苏木精-伊红染色评估视网膜的病理变化。使用商业试剂盒、免疫荧光和 Western blot 检测评估视网膜氧化环境以及细胞凋亡和自噬。结果表明，Gyp-17 对血糖和血脂水平没有显著影响，但与模型组相比，维持了正常的视网膜通透性、生理结构、高抗氧化酶表达以及内核层的厚度。此外，Western blot 分析和 TUNEL 检测表明，Gyp-17 与模型组相比，显著降低了促凋亡相关蛋白的表达，增加了促自噬相关蛋白的表达。免疫荧光共定位显示，Gyp-17 的调节作用可能集中在 Müller 细胞上。这些数据有力地证明，Gyp-17 通过减少 Müller 细胞的凋亡和增加自噬来预防早期 DR。Gyp-17 可能是早期 DR 治疗的候选药物。
