川北医学院学报2025,Vol.40Issue(4):421-424,4.DOI:10.3969/j.issn.1005-3697.2025.04.003
塞来昔布可通过抑制HIF-1α/VEGF信号通路发挥对糖尿病大鼠视网膜病变的保护作用
Protective effect of celecoxib on diabetic retinopathy in rats via inhibiting HIF-1α/VEGF signaling pathway
摘要
Abstract
Objective:To investigate the protective effect of celecoxib on retinopathy(DR)in diabetic rats based on hypoxia-in-ducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)signaling pathway.Methods:30 male Wistar rats were ran-domly divided into normal control group,model group and celecoxib group,with 10 rats in each group.In addition to the normal control group,the other two groups were fed with high-fat diet+streptozotocin intraperitoneal injection to construct DR model.After successful modeling,the celecoxib group was given intragastric administration of celecoxib,while the model group and the normal control group re-ceived equal volumes of solvent once a day for 4 weeks.On the day of drug intervention and 4 weeks after intervention,the body weight and fasting blood glucose of rats were measured.The levels of serum VEGF,interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)were measured by enzyme-linked immunosorbent assay.The pathological changes of rat retina were observed by hematoxylin-eosin(HE)staining.The expression of VEGF and HIF-1α protein in rat retina was detected by Western blot.Results:On the day of drug in-tervention and after 4 weeks of intervention,compared with the normal control group,the body weight of the model group and the cele-coxib group decreased significantly(P<0.05),and the FPG increased significantly(P<0.05).Compared with the normal control group,the levels of serum VEGF,IL-6 and TNF-α in the model group were significantly increased(P<0.05).Compared with the mod-el group,the serum levels of VEGF,IL-6 and TNF-α in the celecoxib group were significantly decreased(P<0.05).HE staining showed that the retinal tissue cells in the normal control group were arranged neatly,the retinal nerve cells in the model group were dis-ordered,and the inner nuclear layer and the outer nuclear layer showed obvious loose changes.Compared with the model group,the ar-rangement of retinal nerve cells in the celecoxib group was closer to normal,and the loose degeneration of the inner nuclear layer and the outer nuclear layer was reduced.Compared with the normal control group,the relative expression of VEGF and HIF-1α protein in the retinal tissue of the model group was significantly increased(P<0.05).Compared with the model group,the relative expression of VEGF and HIF-1α protein in the retinal tissue of the celecoxib group decreased significantly(P<0.05).Conclusion:Celecoxib has a protective effect on retinopathy in diabetic rats,and its mechanism may be related to the inhibition of HIF-1α/VEGF signaling pathway activation.关键词
糖尿病视网膜病变/塞来昔布/血管内皮生长因子/缺氧诱导因子-1αKey words
Diabetic retinopathy/Celecoxib/Vascular endothelial growth factor/Hypoxia-inducible factor-1α分类
临床医学引用本文复制引用
杜鹃,刘媛,杨倩,常瑚,高鸽,马胜男,李娜..塞来昔布可通过抑制HIF-1α/VEGF信号通路发挥对糖尿病大鼠视网膜病变的保护作用[J].川北医学院学报,2025,40(4):421-424,4.基金项目
河北省卫生健康委员会医学科学研究课题计划项目(20251433) (20251433)