通心络抑制KK/Upj-Ay小鼠视网膜组织HIF-1a/VEGF/VEGFR-2表达  

Tongxinluo Inhibits Expression of HIF-1a/VEGF/VEGFR-2 Expression in Retina Tissues of KK/Upj-Ay Mice

作　　者：邢邯英[1] 王超[1] 张会欣 刘敏[1] 王杏[1] 

机构地区：[1]河北省人民医院老年医学重点实验室,石家庄050051 [2]河北以岭医药研究院,石家庄050035

出　　处：《中国实验方剂学杂志》2015年第21期97-101,共5页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家重点基础研究发展计划(973计划)项目(2012CB518600)

摘　　要：目的:观察通心络对自发糖尿病KK/Upj-Ay小鼠视网膜组织缺氧诱导因子-1a(HIF-1a),血管内皮生长因子(VEGF)和血管内皮生长因子受体2(VEGFR2)基因及蛋白表达的影响,探讨通心络对糖尿病视网膜病变的保护机制。方法:40只KK/Upj-Ay小鼠随机分为模型组和通心络低、中、高剂量组(通心络生药1,2,4 g·kg-1,ig给药12周),实验以C57BL/6小鼠为正常组。用血液黏度仪测定全血黏度和血浆黏度、红细胞变形聚集仪测定红细胞聚集指数;应用实时荧光定量PCR法检测各组小鼠视网膜组织中VEGF和VEGFR2的基因表达;Western blot法检测视网膜组织中HIF-1a,VEGF,VEGFR2蛋白的表达。结果:与正常组C57BL/6小鼠比较,模型组小鼠全血黏度、血浆黏度、红细胞聚集指数明显升高(P<0.01);与模型组比较,应用通心络中、高剂量治疗的KK/Upj-Ay小鼠红细胞聚集指数明显降低(P<0.05,P<0.01);高剂量通心络组的低切全血黏度降低(P<0.05),血浆黏度较模型组也显著降低(P<0.01)。模型组小鼠视网膜组织HIF-1a,VEGF,VEGFR2蛋白和VEGF,VEGFR2 mRNA表达较正常组明显增高(P<0.01);通心络ig治疗后,各剂量组HIF-1a,VEGF,VEGFR2 mRNA和蛋白表达水平均较模型组明显下降(P<0.01)。结论:通心络可抑制自发性糖尿病小鼠视网膜组织HIF-1a/VEGF/VEGFR-2信号途径,此作用可能与其改善糖尿病血液流变学相关。Objective： To observe the effect of Tongxinluo on expression of hypoxia inducible factor 1a（ HIF-1a）, vascular endothelial growth factor（ VEGF） and vascular endothelial growth factor receptor 2（ VEGFR2） in retina tissues of KK/Upj-Ay mice with spontaneous diabetes,and explore the protective mechanism of Tongxinluo on diabetic retinopathy. Method： Forty KK / Upj-Ay mice were randomly divided into 4 groups：model group（ n = 10）,Tongxinluo low-dose group（ n = 10,1 g·kg- 1）,median-dose group（ n = 10,2 g·kg- 1）and high-dose group（ n = 10,4 g·kg- 1） group. The mice were given Tongxinluo intragastrically for 12 weeks.C57 BL /6 mice were chosen as normal group（ n = 10）. The whole blood viscosity and plasma viscosity were measured by blood viscometer and red blood cell aggregation index was measured by ektacytometer. The expression levels of VEGF and VEGFR-2 genes in retina tissues of mice were detected with real time fluorescence quantitative PCR method. Western-blot method was used to detect the expression levels of HIF-1a,VEGF,VEGFR2 in retina tissues. Result： Compared with C57 BL /6 mice in the normal group,the whole blood viscosity,the plasma viscosity and the red blood cell aggregation index were all increased in model group（ P〈0. 01）. Compared with the model group,red blood cell aggregation index was significantly decreased in KK / Upj-Ay mice after treatment by middle dose and high dose Tongxinluo（ P〈0. 05,P〈0. 01）,and the whole blood viscosity at low shear rate,and plasma viscosity were also significantly decreased in high-dose Tongxinluo group（ P〈0. 01）. HIF-1a / VEGF /VEGFR-2 proteins and VEGF / VEGFR-2 mRNA expressions in retina tissues of model group mice were significantly higher than those in normal group（ P〈0. 01）,while after treatment with Tongxinluo,HIF-1a / VEGF / VEGFR-2mRNA and protein expressions were significantly lower in low-dose,median-dose and high-dose groups than those in model group（ P〈0. 01）. Conclusion： Tongxinluo m

关 键 词：通心络 糖尿病视网膜病变 血管内皮生长因子 缺氧诱导因子-1a 血管内皮生长因子受体2 

分 类 号：R285.5[医药卫生—中药学]