河北医学2025，Vol.31Issue(12)：1949-1955,7.DOI:10.3969/j.issn.1006-6233.2025.12.03
苦杏仁苷调控cGAS-STING通路对高糖诱导的人视网膜内皮细胞损伤的影响
Effect of Amygdalin Regulating cGAS-STING Pathway on Hyperglucose-Induced Human Retinal Endothelial Cell Injury
摘要
Abstract
Objective:To investigate the protective effect and molecular mechanism of amygdalin on hy-perglucose-induced injury in human retinal endothelial cells(HRECs)through regulation of the cGAS-STING pathway.Methods:An HREC injury model was established using 33 mM high glucose induction.The model was validated through CCK-8 assay,Annexin V/PI double staining,transmission electron microscopy,and ROS level detection to assess cell proliferation,apoptosis,mitochondrial morphology,and intracellular ROS levels.HRECs were treated with 100μM amygdalin to intervene in hyperglucose-induced injury.Chan-ges in cell survival,IFN-α secretion,and cGAS/STING mRNA expression were detected using Annexin V/PI double staining,ELISA,and RT-qPCR.Subsequently,the STING inhibitor C176(2μM)and cGAS agonist RU.521(10μM)were applied,and the signaling pathway affected by amygdalin was examined through RT-qPCR,immunofluorescence,Western blot,and Transwell assays.The cGAS gene was knocked down using siRNA,and the alternative TLR4/MyD88 pathway was excluded using the TLR4 inhibitor TAK-242.Re-sults:Treatment with 33 mM high glucose for 48 hours reduced cell viability,increased apoptosis,induced mitochondrial damage,elevated ROS levels,upregulated Cleaved caspase-3 expression,and increased the Bax/Bcl-2 protein expression ratio(all P<0.05).Treatment with 100μM amygdalin significantly improved cell survival,restored LDH levels,upregulated cGAS/STING mRNA expression,promoted STING Golgi translocation,and enhanced IFN-α secretion(all P<0.05).Amygdalin activated the cGAS-STING pathway,leading to increased cell viability,elevated p-TBK1/p-IRF3 expression,and reduced apoptosis--effects that were reversed by C176(all P<0.05).Functional recovery experiments showed that amygdalin restored trans-epithelial electrical resistance(TEER)values,increased cell junction density,reduced secretion of in-flammatory factors IL-6 and TNF-α,and decreased NO levels(all P<0.05).Knocking down cGAS with siRNA increased apoptosis and SA-β-gal positivity again,while no significant changes were observed in TLR4 pathway-related indicators.Conclusion:Amygdalin specifically activates the cGAS-STING pathway,inhibits mitochondrial damage and DNA breakage,and reduces inflammatory responses,thereby ameliorating high glucose-induced injury in retinal endothelial cells.This effect is independent of the TLR4/MyD88 signa-ling axis,providing a new therapeutic target for diabetic retinopathy.关键词
苦杏仁苷/cGAS-STING通路/高糖损伤/视网膜内皮细胞Key words
Amygdalin/cGAS-STING pathway/High sugar damage/Retinal endothelial cells引用本文复制引用
王倩,陈静,李元伟..苦杏仁苷调控cGAS-STING通路对高糖诱导的人视网膜内皮细胞损伤的影响[J].河北医学,2025,31(12):1949-1955,7.基金项目
山东省医药卫生科技发展计划项目,(编号:2021WS094) （编号:2021WS094）
