柿叶黄酮对KKAy小鼠视网膜病变CTGF,VEGF,HIF-1α的影响  

Effect of Flavonoid from Diospyros kaki Leaf on Expressions of CTGF,VEGF,HIF-1α in Retina of KKAy Mice

作　　者：邓振德[1] 黄勇志[1] 潘丽莎[1] 颜鲁宁[1] 佘啸[1] 李丽[1] 郑妮[2] 

机构地区：[1]中国人民解放军第303医院,南宁530021 [2]深圳大学,广东深圳518000

出　　处：《中国实验方剂学杂志》2017年第2期115-119,共5页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：广西省代谢性疾病研究重点实验室开放基金课题(2012-181h-02)

摘　　要：目的:观察柿叶黄酮对KKAy小鼠糖尿病视网膜病变(DR)结缔组织生长因子(connective tissue growth factor,CTGF),血管内皮生长因子(vascular endothelial growth factor,VEGF),以及低氧诱导因子1α(hypoxia-inducible factor-1α,HIF-1α)的影响及其保护机制。方法:取30只8周龄C57BL6/J小鼠作为正常组,另取150只8周龄雄性KKAy小鼠随机分为KKAy模型组、柿叶黄酮高、中、低剂量组、羟苯磺酸钙组,每组各30只小鼠。柿叶黄酮高、中、低剂量组分别给予柿叶黄酮(50,100,200 mg·kg^(-1)·d^(-1))ig,羟苯磺酸钙组给予羟苯磺酸钙230 mg·kg^(-1)·d^(-1)ig,KKAy模型组及正常组给予等量生理盐水灌胃,共16周。检测血糖(FBG),糖化血红蛋白(GHb),血液流变学指标;酶联免疫吸附测定(ELISA)法检测法检测视网膜内CTGF,VEGF,蛋白质免疫印迹(Western blot)法检测HIF-1α的表达。苏木素-伊红(HE)染色观察视网膜组织损伤情况,TUNEL检测视网膜细胞凋亡程度。结果:与正常组小鼠比较,KKAy模型组小鼠的血糖显著升高,GHb的水平显著降低(P<0.01),视网膜CTGF,VEGF和HIF-1α的表达显著增加(P<0.01),视网膜组织结构损伤严重。经过16周给药,与KKAy模型组比较,柿叶黄酮中、高剂量组小鼠的血糖显著降低(P<0.01),GHb的水平显著提高(P<0.01),视网膜CTGF,VEGF和HIF-1α的表达及明显减少(P<0.05,P<0.01),视网膜组织损伤情况改善明显。结论:柿叶黄酮对KKAy小鼠DR具有保护作用,其机制可能与调节视网膜内CTGF,VEGF和,HIF-1α的表达有关。Objective： To investigate the protection effects of flavonoid from Diospyros kaki leaf（ FDL）on expressions of connective tissue growth factor（ CTGF）,vascular endothelial growth factor（ VEGF）,hypoxiainducible factor-1α（ HIF-1α） in the diabetic retinopathy（ DR） of KKAy mice. Method： Take 30 C57BL6 / J mice as normal control group,one hundred and fifty male KKAy rats were randomly divided into five groups： KKAy model group,FDL high-dose group,FDL medium-dose group,FDL low-dose group and Calcium Dobesilate group consist of 30 mice per group, high-, medium-, low-dose groups were administrated with 200, 100,50 mg·kg^-1·d^-1dose of FDL,Calcium Dobesilate group was given 230 mg·kg^-1·d^-1Calcium Dobesilate,normal control group and KKAy model group received equal volume of saline. After 16 weeks,fasting blood glucose（ FBG）,glycosylated hemoglobin（ GHb）,the whole blood viscosity and plasma viscosity were detected. The expressions of CTGF, VEGF were examined by ELISA,HIF-1α were dected by Western blot and located by immunohistochemistry. Etinal apoptosis was detected by TUNEL staining. Result： Compared to normal control group,the FBG increased markedly,the GHb reduced obviously,the expression of CTGF,VEGF,HIF-1α and TUNEL-positive nuclei number in the DR were significantly higher increased obviously in the KKAy model group（ P〈0. 01）. Compared to the KKAy model group the GHb was markedly increased（ P〈0. 01）,the expression of CTGF,VEGF,HIF-1α and TUNEL-positive nuclei number in the FDL high-dose and medium-dose group reduced obviously（ P〈0. 01）. Conclusion： The FDL can significantly repair DR and its mechanism may be actualized by regulationg CTGF,VEGF,HIF-1α in retinopathy.

关 键 词：柿叶黄酮 糖尿病视网膜病变 结缔组织生长因子 血管内皮生长因子 低氧诱导因子1Α 

分 类 号：R285.5[医药卫生—中药学]