眼科新进展2026，Vol.46Issue(9)：682-688,7.DOI:10.13389/j.cnki.rao.2026.0118
红景天苷调控HIF-1α/BNIP3通路对缺氧诱导的病理性眼部血管新生的抑制作用
Inhibitory effect of salidroside on hypoxia-induced pathological ocular angio-genesis by regulating the hypoxia-inducible factor-1α/adenovirus E1B 19 kDa-interacting protein 3 pathway
摘要
Abstract
Objective To investigate the effect of salidroside on pathological ocular angiogenesis in an oxygen-in-duced retinopathy(OIR)mouse model by regulating the hypoxia-inducible factor-1α(HIF-1α)/adenovirus E1B 19 kDa-in-teracting protein 3(BNIP3)signaling pathway.Methods In animal experiments,24 specific pathogen-free C57 mice were randomly divided into four groups using a random number table method:normal control group,OIR model group,salidroside treatment group,and bevacizumab positive control group,with 6 mice in each group.Except for the normal control group,mice in the other groups were exposed to hyperoxia(75.0％±2.0％oxygen)from day 7 to day 12 and then returned to normal room air(21.0％oxygen)until day 17 to establish the OIR model.Mice in the normal control group were raised in room air without any intervention.Mice in the OIR model group received no intervention after modeling.Mice in the salidro-side treatment group received daily intragastric administration of salidroside at 50 mg·kg-1 from day 12 to day 17 after modeling.Mice in the bevacizumab positive control group received a single intravitreal injection of 1 μL bevacizumab(con-taining 25 μg active ingredient)on day 12 after modeling.Immunofluorescence staining was used to detect the expression of platelet-endothelial cell adhesion molecule(CD31)in the retina.Enzyme-linked immunosorbent assay(ELISA)was em-ployed to measure the levels of vascular endothelial growth factor(VEGF)and angiopoietin-like protein 4(ANGPTL4)in retinal tissues.Transmission electron microscopy was utilized to observe mitochondrial morphology in retinal vascular endo-thelial cells.In cell experiments,hypoxic human umbilical vein endothelial cells(HUVECs)were cultured and divided into four groups:normoxia control group,hypoxia model group,hypoxia+salidroside intervention group,and hypoxia+sali-droside+deferoxamine(an HIF-1α stabilizer)antagonism group.Transwell assay was used to assess the migration ability,whereas tube formation assay was employed to evaluate the tube-forming ability of cells in each group.Western blot analysis was performed to detect the relative expression levels of dynamin-related protein 1(DRP1),phosphorylated DRP1(p-DRP1)at serine 616(Ser616),p-DRP1 Ser637,mitofusin 2(MFN2),HIF-1α,and BNIP3 proteins in both mouse retinal tis-sues and HUVECs.Results Compared with the normal control group,the OIR model group showed significantly higher numbers of CD31-positive retinal microvessels,significantly elevated VEGF and ANGPTL4 levels,and increased mitochondri-al fission,with all differences being statistically significant(all P＜0.01).Compared with the OIR model group,the above indicators were significantly reversed in both the salidroside treatment group and the bevacizumab positive control group,with all differences showing statistical significance(all P＜0.01).In cell experiments,salidroside significantly inhibited hy-poxia-induced HUVEC migration and tube-forming abilities,with statistically significant differences(all P＜0.01),and this effect was partially antagonized by deferoxamine.Western blot analysis revealed that salidroside significantly down-regula-ted the relative expression of HIF-1α,BNIP3,and the pro-fission protein p-DRP1 Ser616 in mouse retinal tissues and HU-VECs under hypoxic conditions,with all differences being statistically significant(all P＜0.01),while increasing the relative expression of the anti-fission proteins p-DRP1 Ser637 and MFN2,and all differences were statistically significant(all P＜0.05).Conclusion Salidroside inhibits hypoxia-induced pathological ocular angiogenesis by suppressing the HIF-1α/BNIP3 signaling pathway and reducing mitochondrial fission.关键词
红景天苷/缺氧诱导因子-1α/腺病毒E1B 19 kDa相互作用蛋白3信号通路/线粒体裂变/病理性眼部血管新生Key words
salidroside/hypoxia-inducible factor-1α/adenovirus E1B 19 kDa-interacting protein 3 signaling pathway/mitochondrial fission/pathological ocular angiogenesis分类
医药卫生引用本文复制引用
李娜,崔丽珺,李薪柳,闫鸿燕,罗一青..红景天苷调控HIF-1α/BNIP3通路对缺氧诱导的病理性眼部血管新生的抑制作用[J].眼科新进展,2026,46(9):682-688,7.基金项目
青海省科技计划项目(编号:2023-ZJ-768) （编号:2023-ZJ-768）
朗视界沐光明-中青年眼科科研项目(编号:BCF-KH-YK-20240906-01) （编号:BCF-KH-YK-20240906-01）
2024年青海省"昆仑英才·高端创新创业人才"项目 （）
