中国临床药理学与治疗学2025,Vol.30Issue(8):1017-1025,9.DOI:10.12092/j.issn.1009-2501.2025.08.002
LOX-1促进低氧诱导的内皮细胞自噬与凋亡
LOX-1 promotes hypoxia-induced autophagy and apoptosis in endo-thelial cells
摘要
Abstract
AIM:To investigate the role of lectin-like oxidized low-density lipoprotein receptor-1(LOX-1)in hypoxia-induced autophagy and apopto-sis in endothelial cells.METHODS:Human umbili-cal vein endothelial cells(HUVECs)were exposed to hypoxia(1%O2)for varying durations(0,6,12,24 h)to evaluate autophagy and apoptosis levels.LOX-1 was further intervened to explore its effects on autophagy and apoptosis.GFP-LC3B adenovirus in-fection was observed under fluorescence microsco-py to assess LC3B expression.Autophagosomes were detected by transmission electron microscopy(TEM).LOX-1 mRNA levels were measured using re-al-time PCR.Protein expression of LOX-1,LC3Ⅱ/Ⅰ,Beclin-1,Atg5,cleaved-caspase 3,Bax,and Bcl-2 was analyzed by Western blot.Reactive oxygen spe-cies(ROS)levels were quantified using the DCFH-DA fluorescent probe.Apoptosis was assessed via Hoechst staining and flow cytometry(Annexin V-PI double staining).RESULTS:Hypoxia(1%O2,24 h)significantly increased LC3Ⅱ puncta under fluores-cence microscopy,upregulated LC3Ⅱ/Ⅰ protein ex-pression,and induced autophagosome formation observed by TEM.Hypoxia elevated ROS produc-tion and promoted apoptosis.LOX-1 mRNA and protein expression were upregulated in hypoxic HU-VECs.LOX-1 siRNA intervention markedly reversed hypoxia-induced autophagy,downregulating au-tophagy-related proteins(Beclin-1,Atg5,LC3Ⅱ/Ⅰ).LOX-1 siRNA also suppressed ROS generation and inhibited apoptosis,as evidenced by decreased ex-pression of cleaved-caspase 3 and Bax,and in-creased Bcl-2 levels.CONCLUSION:Hypoxia in-duced upregulation of LOX-1 expression to produce ROS,thereby promoting autophagy and apoptosis in endothelial cells.关键词
植物凝集素样氧化性低密度脂蛋白受体-1/低氧/自噬/凋亡/内皮细胞Key words
lectin-like oxidized low-density lipo-protein receptor-1/hypoxia/autophagy/apoptosis/endothelial cell分类
医药卫生引用本文复制引用
李燕飞,黄灿,罗平,何芳,胡长平..LOX-1促进低氧诱导的内皮细胞自噬与凋亡[J].中国临床药理学与治疗学,2025,30(8):1017-1025,9.基金项目
国家自然科学基金(82173817,82241025) (82173817,82241025)
湖南省卫生健康委科研计划课题资助项目(D202313016976) (D202313016976)
中国医药教育协会2023年"临床用药卫生技术评估"专项课题资助项目(2023WSJSPG-ZXKT-21) (2023WSJSPG-ZXKT-21)