眼科新进展2025,Vol.45Issue(3):196-201,6.DOI:10.13389/j.cnki.rao.2025.0035
基于HIF-1α通路探讨芍药苷改善糖尿病视网膜病变引起的组织和细胞损伤的机制
The mechanism of paeoniflorin improving tissue and cell damage caused by diabetes retinopathy through the HIF-1α pathway
摘要
Abstract
Objective To investigate the mechanisms by which paeoniflorin improves tissue and cell damage caused by diabetic retinopathy(DR)through the hypoxia-induced factor-1α(HIF-1α)pathway.Methods Thirty rats were ran-domly divided into a control group(10 normal rats),a DR group(10 diabetic model rats)and a paeoniflorin group(10 dia-betic model rats given 80 mg·kg-1 paeoniflorin by gavage).Rat retinal microvascular endothelial cells(rRMECs)were di-vided into a control group(cultured with 5 mmol·L-1 glucose),a high glucose group(cultured with 30 mmol·L-1 glu-cose)and a paeoniflorin group(cultured with 30 mmol·L-1 glucose and 20 mol·L-1 paeoniflorin).The three groups of cells were all cultured for 24 h.Fasting blood glucose was measured by a glucose meter.Hematoxylin and eosin(HE)stai-ning was used to detect the retinal histopathological structure.The levels of HIF-1α and vascular endothelial growth factor(VEGF)proteins and mRNAs in retinal tissues and rRMECs were detected by Western blotting and real time quantitative polymerase chain reaction(RT-qPCR).The proliferative ability of rRMECs was detected by the EdU kit.The serum levels of total cholesterol(TC),triglyceride(TG),low density cholesterol(LDL-C),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in retinal tissues and rRMECs were detected by kits.The activity and invasive ability of rRMECs were measured by CCK-8 and Transwell assay,respectively.The levels of HIF-1α and VEGF proteins in rRMECs were detected by immunofluorescence staining.Results Compared with those in the DR group,the fasting blood glucose,TC,TG and LDL-C levels in the paeoniflorin group were significantly decreased(all P<0.05).The retinal tissue was loose with an un-clear boundary in the DR group,compared with that in the control group.The retinal tissue in the paeoniflorin group was less loose with a clearer boundary than that in the DR group.The levels of HIF-1α and VEGF proteins and mRNAs,TNF-αand IL-6 in retinal tissues of the DR group were significantly higher than those of the control group(all P<0.05).The lev-els of HIF-1α and VEGF proteins and mRNAs,TNF-α and IL-6 in retinal tissues of the paeoniflorin group were significantly lower than those in the DR group(all P<0.05).The activity,proliferation and invasive abilities of rRMECs in the high glu-cose group were higher than those in the control group(all P<0.05).Compared with those in the high glucose group,rRMECs in the paeoniflorin group showed decreased cell activity,proliferation and invasive abilities(all P<0.05).The lev-els of HIF-1α and VEGF proteins and mRNAs,TNF-α and IL-6 in the rRMECs of the high glucose group were higher than those of the control group(all P<0.05).The levels of HIF-1α and VEGF proteins and mRNAs,TNF-α and IL-6 in the rRMECs of the paeoniflorin group were lower than those of the high glucose group(all P<0.05).Conclusion Paeoni-florin can down-regulate the HIF-1α/VEGF pathway to improve the inflammatory injury of the retinal tissue and inhibit rRMEC activity,proliferation and invasive abilities in DR rats,thereby preventing angiogenesis and reducing the incidence of DR.关键词
糖尿病视网膜病变/缺氧诱导因子-1α通路/芍药苷/视网膜微血管内皮细胞/炎性因子Key words
diabetic retinopathy/hypoxia-induced factor-1α pathway/paeoniflorin/retinal microvascular endothelial cells/inflammatory factors分类
临床医学引用本文复制引用
刘霞,易勉,李灵,岳江,赵静,罗杏梅,黄洁..基于HIF-1α通路探讨芍药苷改善糖尿病视网膜病变引起的组织和细胞损伤的机制[J].眼科新进展,2025,45(3):196-201,6.基金项目
湖南省卫生健康委员会科研项目(编号:20230273) (编号:20230273)