京尼平苷对糖尿病视网膜病变大鼠视网膜微血管生成的影响及其机制  

Effect of geniposide on retinal microangiogenesis in rats with diabetic retinopathy and its mechanism

作　　者：苏杰 杨馥宇 李猛 蒋利生 SU Jie;YANG Fuyu;LI Meng;JIANG Lisheng(Department of Ophthalmology,Affiliated Hospital of North China University of Science and Technology,Tangshan 063000,Hebei Province,China;Department of Ophthalmology,Luanzhou People’s Hospital,Tangshan 063700,Hebei Province,China)

机构地区：[1]华北理工大学附属医院眼科,河北省唐山市063000 [2]滦州市人民医院眼科,河北省唐山市063700

出　　处：《眼科新进展》2023年第9期703-707,711,共6页Recent Advances in Ophthalmology

基　　金：河北省教育厅高等学校科学技术研究项目(编号:QN2020110);河北省医学科学研究课题计划(编号:20220187)。

摘　　要：目的探讨京尼平苷(Gen)对糖尿病视网膜病变(DR)大鼠视网膜微血管生成的影响及其机制。方法取6周龄SPF级雄性Wistar大鼠50只,将眼部正常的大鼠随机分为正常组、模型组、Gen低剂量组、Gen高剂量组和羟苯磺酸钙组,每组10只。除正常组外,其余组大鼠通过高糖高脂饲料饲养联合链脲佐菌素诱导DR大鼠模型。模型构建成功后立即进行药物干预。Gen低剂量组和Gen高剂量组大鼠分别以25 mg·kg^(-1)和100 mg·kg^(-1)Gen灌胃,羟苯磺酸钙组大鼠给予5.8 mg·kg^(-1)羟苯磺酸钙灌胃,而正常组和模型组大鼠灌胃等量溶剂,每天1次,连续4周。给药期间正常组大鼠继续喂养普通饲料,其余各组大鼠继续喂养高糖高脂饲料。ELISA检测大鼠血清中血管内皮生长因子(VEGF)和可溶性血管内皮生长因子受体1(sFlt-1)的含量;HE染色观察大鼠视网膜组织病理学变化;过碘酸雪夫染色观察大鼠视网膜微血管生成情况;Western blot检测大鼠视网膜组织中VEGF、缺氧诱导因子-1α(HIF-1α)、细胞间黏附分子-1(ICAM-1)、sFlt-1等蛋白表达水平。结果药物干预结束(第4周),模型组大鼠血清中VEGF含量高于正常组,sFlt-1含量低于正常组,差异均有统计学意义(均为P<0.001)。Gen高剂量组和羟苯磺酸钙组大鼠血清中VEGF含量低于模型组,sFlt-1含量高于模型组,差异均有统计学意义(均为P<0.001);而Gen低剂量组大鼠以上指标与模型组相比,差异均无统计学意义(均为P>0.05)。药物干预结束(第4周),正常组大鼠视网膜组织形态正常,内核层与外核层细胞排列整齐。模型组和Gen低剂量组大鼠视网膜组织内核层与外核层细胞排列松散,神经节细胞减少,毛细血管充血。Gen高剂量组和羟苯磺酸钙组大鼠视网膜组织内核层与外核层细胞排列趋于正常,神经节细胞较模型组明显增多。药物干预结束(第4周),模型组大鼠视网膜组织血管管径不均,出现节段性膨大,�Objective To investigate the effect of geniposide(Gen)on retinal microangiogenesis in rats with diabetic retinopathy(DR)and its mechanism.Methods Fifty 6-week-old SPF male Wistar rats with normal eyes were randomly divided into the normal group,model group,low-dose Gen group,high-dose Gen group,and calcium dobesilate group,with 10 rats in each group.Except for the normal group,rats in the other groups were fed high-sugar and high-fat diets and induced by streptozotocin to establish the DR rat models.After modeling,drug intervention was carried out immediately.Rats in the low-and high-dose Gen groups were given 25 mg·kg^(-1) and 100 mg·kg^(-1) Gen intragastrically,rats in the calcium dobesilate group were given 5.8 mg·kg^(-1) calcium dobesilate intragastrically,while rats in the normal and model groups were given the same amount of solvent intragastrically,once a day for 4 weeks.During the drug administration period,rats in the normal group continued to be fed normal diets,and rats in the other groups continued to be fed high-sugar and high-fat diets.Levels of vascular endothelial growth factor(VEGF)and soluble VEGF receptor 1(sFlt-1)in serum were measured by the enzyme-linked immunosorbent assay.Retinal pathological changes were exhibited by hematoxylin-eosin staining.Retinal microangiogenesis was revealed by periodic acid-Schiff staining.The expression levels of VEGF,hypoxia-inducible factor-1α(HIF-1α),intercellular adhesion molecule-1(ICAM-1),and sFlt-1 in the retina were measured by Wes tern blot.Results At the end of drug intervention(week 4),serum VEGF level in the model group was higher than that in the normal group,while sFlt-1 level was lower than that in the normal group(both P<0.001);serum VEGF level in the high-dose Gen and calcium dobesilate groups was lower than that in the model group,while sFlt-1 level was higher than that in the model group(all P<0.001);there were no significant differences in the above indexes between the low-dose Gen group and the model group(all P>0.05).At the end of drug

关 键 词：糖尿病视网膜病变 京尼平苷 血管内皮生长因子 可溶性血管内皮生长因子受体1 微血管生成 

分 类 号：R774[医药卫生—眼科]