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

作　　者：杜鹃 刘媛[1] 杨倩[1] 常瑚 高鸽 马胜男 李娜 DU Juan;LIU Yuan;YANG Qian;CHANG Hu;GAO Ge;MA Sheng-nan;LI Na(Department of Ophthalmology,Baoding No.1 Central Hospital,Baoding 071000,Hebei,China)

机构地区：[1]保定市第一中心医院眼科,河北保定071000

出　　处：《川北医学院学报》2025年第4期421-424,共4页Journal of North Sichuan Medical College

基　　金：河北省卫生健康委员会医学科学研究课题计划项目(20251433)。

摘　　要：目的:基于缺氧诱导因子-1α(HIF-1α)/血管内皮生长因子(VEGF)信号通路探讨塞来昔布对糖尿病大鼠视网膜病变(DR)的保护作用。方法:将30只雄性Wistar大鼠分为正常对照组、模型组与塞来昔布组,每组各10只。除正常对照组外,其余两组均采用高脂饲料喂养+链脲佐菌素腹腔注射的方法构建DR模型。建模成功后,塞来昔布组予以塞来昔布灌胃干预;模型组及正常对照组则予以等量溶媒灌胃,1次/d,连续4周。于药物干预当天和干预4周后,检测大鼠体质量和空腹血糖,采用酶联免疫吸附法对大鼠血清VEGF、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)水平进行测定,采用苏木素-伊红(HE)染色观察大鼠视网膜组织病理情况;采用Western blot法观察大鼠视网膜组织VEGF、HIF-1α蛋白表达水平。结果:药物干预当天及干预4周后,与对照组比较,模型组及塞来昔布组体质量均下降(P<0.05),空腹血糖(FPG)增高(P<0.05)。与对照组比较,模型组血清VEGF、IL-6、TNF-α水平上升(P<0.05);与模型组比较,塞来昔布组血清VEGF、IL-6、TNF-α水平下降(P<0.05)。HE染色显示,正常对照组大鼠视网膜组织细胞排列整齐;模型组大鼠视网膜组织神经细胞排列紊乱,内核层与外核层呈现出明显的疏松样变;与模型组比较,塞来昔布组视网膜神经细胞排列趋于正常,内核层与外核层疏松样变减轻。与对照组比较,模型组血清大鼠视网膜组织VEGF、HIF-1α蛋白相对表达量上升(P<0.05);与模型组比较,塞来昔布组视网膜组织VEGF、HIF-1α蛋白相对表达量下降(P<0.05)。结论:塞来昔布对糖尿病大鼠视网膜病变具有保护作用,其机制可能与抑制HIF-1α/VEGF信号通路激活有关。Objective:To investigate the protective effect of celecoxib on retinopathy(DR)in diabetic rats based on hypoxia-inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)signaling pathway.Methods:30 male Wistar rats were randomly 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 received 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-1αprotein in rat retina was detected by Western blot.Results:On the day of drug intervention and after 4 weeks of intervention,compared with the normal control group,the body weight of the model group and the celecoxib 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-αin the model group were significantly increased(P<0.05).Compared with the model group,the serum levels of VEGF,IL-6 and TNF-αin 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 disordered,and the inner nuclear layer and the outer nuclear layer showed obvious loose changes.Compared with the model group,the arrangement of retinal nerve cells in the celecoxib group was closer to normal,and the loose degeneration of the inner nuclear layer and t

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-1Α 

分 类 号：R774.13[医药卫生—眼科]