瑞舒伐他汀钙通过下调血管内皮生长因子的表达抑制斑马鱼血管发育

Rosuvastatin calcium inhibits the vascular development of zebrafish by down regulating the expression levels of vascular endothelial growth factor

目的:通过研究瑞舒伐他汀钙对斑马鱼血管发育的影响,探讨瑞舒伐他汀钙抑制血管的作用机制。方法:将瑞舒伐他汀钙处理的斑马鱼胚胎作为实验组,以0.5%二甲亚砜处理的胚胎作为对照组。从受精卵形成后0.5h开始刺激,受精后24h观察药物对斑马鱼血管发育的影响。使用荧光显微镜观察新生血管状态,记录血管缺失数目,分别从受精后0、6、12和24h药物处理后的斑马鱼胚胎中提取总的RNAs,采用实时定量逆转录聚合酶链反应(RT-PCR)检测血管内皮生长因子A(vascular endothelial growth factor A,VEGF-A)的表达变化。结果:瑞舒伐他汀钙可明显抑制斑马鱼血管发育,且在0.01～0.08nmol/L浓度范围内抑制作用与药物浓度成正比。实验组较对照组VEGF-A表达量降低,在药物作用的24h具有显著性差异(P<0.05)。结论:瑞舒伐他汀钙可通过减少VEGF-A的表达抑制斑马鱼血管发育。

Objective： To observe the effect of rosuvastatin calcium on the vascular development of zebrafish,and investi- gate the inhibition mechanism involved. Methods： The zebrafish embryos incubated with rosuvastatin calcium were identified as the experimental group. Meanwhile,the embryos immersed in 0.5 % dimethyl sulfoxide（DMSO） were identified as the control group. The embryos were treated with drugs at 0.5 hour post fertilization（hpf） stage of development. After 24 hpf of exposure to the drugs,the numbers of intersegmental vessels of embryos were inspected and recorded by fluorescence microscope. Total RNAs were extracted from 0,6,12 and 24 hpf zebrafish embryos. The expression levels of vascular endothelial growth factor A （VEGF-A） were examined by real time quantitative reverse transcription polymerase chain reaction（RT-PCR）. Results： The growth of intersegmental vessels of zebrafish was significantly inhibited by rosuvastatin calcium. And the inhibition effect of ro- suvastatin calcium was dose-dependent in the concentration range of 0.01-0.08 nmol/L. Compared with that of the control group, the expression levels of VEGF A was reduced in the experiment group, and it was significantly different at 24 hpf（P〈0.05）. Conclusion：Rosuvastatin calcium could inhibit the vascular development of zebrafish by down regulating the expression levels of VEGF-A