丹参酮ⅡA下调血管内皮生长因子及其受体抑制斑马鱼血管发育  

Tanshinone ⅡA down-regulates the expression of VEGF and VEGFR2 and inhibits vascular development in zebrafish

作　　者：刘博[1] 吕慧[1] 王国坤[1] 吴峰[1] 李松华[1] 秦永文[1] 

机构地区：[1]上海交通大学医学院附属新华医院心内科,上海200092

出　　处：《解剖学杂志》2014年第2期178-180,216,共4页Chinese Journal of Anatomy

摘　　要：目的：研究丹参酮ⅡA对斑马鱼血管内皮生长因子（VEGF）及其受体（VEGFR2）和血管发育的影响.方法：将丹参酮ⅡA处理的胚胎作为实验组,以0.5％二甲基亚砜（DMSO）作为对照组.受精后24 h（24 hpf）观察药物对转基因斑马鱼血管发育的影响,荧光显微镜观察新生血管状态,记录血管长度.分别从0、6、12和24 hpf时相的药物处理后的斑马鱼胚胎中提取总的RNA,采用实时定量RT-PCR方法检测VEGF及VEGFR2的表达变化.结果：丹参酮ⅡA可明显抑制斑马鱼血管发育,且在100 μg/ml和200 μg/ml浓度下可发挥抑制作用,无浓度递增关系.实验组较对照组VEGF及VEGFR2表达量降低,在药物作用的12 hpf和24 hpf具有显著性差异.结论：丹参酮ⅡA可下调VEGF及VEGFR2的表达,抑制斑马鱼血管发育.Objective： To investigate the effect of tanshinone ⅡA on the expression of VEGF and VEGFR2 and vascular development in zebrafish. Methads： Zebrafish embryos were treated with Tanshinone ⅡA which was dissolved in 0.5% dimethyl sulfoxide （DMSO） at different concentrations as an experimental group （exp）, and those treated with only 0.5 DMSO were used as a control group （con）. The embroys were treated before the 1 hour postfertilization （hpf） stage of development and incubated in 24-well plates at 28℃ with one drug concentration for 24 hours before images were taken. The length of the intersegmental vessels was valued under a fluorescence microscope. Total RNAs were extracted from 0, 6, 12 hpf and 24 hpf zebrafish embryos. Real-time quantitative RT-PCR was used to analyze mRNA expression profiles of VEGF and VEGFR2. T-test was used to evaluate the difference between the exp and con groups. RNA data were analyzed by 2 △△α, method. Results： Tanshinone ⅡA inhibited blood vessel formation was indicated by the slower growth of the zebrafish intersegmental vessels. This inhibition was not concentration-dependent. Tanshinone ⅡA exposure significantly down- regulated the expression of VEGF and VEGFR2 in zebrafish embryos at 12 hpf and 24 hpf. Conclusion： Our results demonstrate that tanshinone ⅡA be effective in inhibiting angiogenesis in zabrafish embryos, supporting the use of tanshinone ⅡA as a prospective agent to inhibit tumor angiogenesis.

关 键 词：血管生成 血管内皮生长因子 斑马鱼 

分 类 号：R735.2[医药卫生—肿瘤]