眼科新进展2025,Vol.45Issue(10):761-768,8.DOI:10.13389/j.cnki.rao.2025.0131
山柰酚调控Notch1/Hes1信号通路对视网膜静脉阻塞继发黄斑水肿的影响
Kaempferol attenuates macular edema secondary to retinal vein occlusion via modulation of the Notch1/Hes1 signaling pathway
摘要
Abstract
Objective To investigate the mechanism of kaempferol(KPF)in the treatment of macular edema sec-ondary to retinal vein occlusion(RVO-ME).Methods RVO model was established in SD rats using photocoagulation.Twenty SD rats were randomly divided into:Control group(normal rats,saline injection),Model group(RVO model rats,saline injection),Low KPF group[RVO model rats,KPF injection(8 mg·kg-1·d-1)],High KPF group[RVO model rats,KPF injection(16 mg·kg-1·d-1)],with 5 rats per group for 14 days.Fundus photography observed retinal vessels;HE staining evaluated retinal structural changes.HRMECs were randomly divided into:control group(no intervention),CoCl2 group(300 μmol·L-1 CoCl2),Low-dose KPF group(300 μmol·L-1 CoCl2+20 μmol·L-1 KPF),High-dose KPF group(300 μmol·L-1 CoCl2+30 μmol·L-1 KPF)and pathway inhibitor group(DAPT group)(300 μmol·L-1 CoCl2+20 μmol·L-1 DAPT),with 24-hour intervention.CCK-8 assay detected cell viability;Scratch test measured cell migration rate;ELISA quantified inflammatory factors[interleukin(IL)-6,tumor necrosis factor(TNF)-α];FITC-dextran assay evalu-ated endothelial monolayer permeability;Immunofluorescence detected zonula occludens(ZO)-1 expression;Western blot and RT-PCR measured protein and mRNA levels of ZO-1,Occludin,Notch1,and Hes1.Results Fundus photography showed interrupted venous blood flow and retinal edema in Model group,alleviated by KPF.HE staining revealed disorder-ed retinal arrangement and severe edema in the Model group,improved by KPF.Compared with CoCl2 group,Low-and High-dose KPF groups showed reduced cell migration rate,increased cell vitality(both P<0.05),IL-6 and TNF-α levels de-creased in Low-and High-dose KPF groups and DAPT group(all P<0.05),permeability coefficient decreased in Low-and High-dose KPF groups and DAPT group(all P<0.05),ZO-1 expression increased in Low-and High-dose KPF groups and DAPT group(all P<0.05),ZO-1 and Occludin protein/mRNA levels increased;Notch1 and Hes1 protein/mRNA levels de-creased in Low-and High-dose KPF groups and DAPT group(all P<0.05).Conclusion KPF treat RVO-ME by inhibiting the Notch1/Hes1 pathway,exerting anti-inflammatory effects and improving intercellular tight junctions.关键词
KPF/Notch/紧密连接/炎症/HRMECs/视网膜静脉阻塞/黄斑水肿Key words
kaempferol/Notch/tight junction/inflammation/HRMECs/retinal vein occlusion/macular edema分类
医药卫生引用本文复制引用
刘梦婷,葛申,郭一俊,李伟博,吴文思,苏晶..山柰酚调控Notch1/Hes1信号通路对视网膜静脉阻塞继发黄斑水肿的影响[J].眼科新进展,2025,45(10):761-768,8.基金项目
国家自然科学基金项目(编号:81904257) (编号:81904257)
上海市科学技术委员会医学创新项目(编号:21Y11923100) (编号:21Y11923100)
浦东新区卫生健康委员会项目(编号:2025-PWDL-15) (编号:2025-PWDL-15)