力达霉素通过下调VEGF表达抑制斑马鱼胚胎血管生成  

Lidamycin inhibits angiogenesis of zebrafish embryo via down-regulation of VEGF

作　　者：丁丽丽[1,2] 刘明[1] 张胜华[3] 赵向忠[1,2] 吴宁[1,2] 陈雷[1,2] 王广建[1] 林秀坤[1] 

机构地区：[1]中国科学院海洋研究所,山东青岛266071 [2]中国科学院研究生院,北京100049 [3]中国医学科学院医药生物技术研究所,北京100050

出　　处：《药学学报》2010年第4期456-461,共6页Acta Pharmaceutica Sinica

基　　金：中国科学院创新基地项目(KSCX2-YW-104;KZCX2-YW-209);山东省科技发展计划项目(2007GG10005002)

摘　　要：本研究采用斑马鱼胚胎模型研究力达霉素在整体动物水平对血管生成的影响。力达霉素处理胚胎后,利用形态学观察、血管染色法、转基因斑马鱼检测其对胚胎血管生成影响,以荧光定量PCR和蛋白免疫印迹法检测VEGF基因的表达情况。结果显示:力达霉素处理后,胚胎出现心包水肿、血流速度减缓等症状;血管生长率降低,肠下静脉生成受到抑制。荧光定量PCR和蛋白免疫印迹检测表明,力达霉素对胚胎的VEGFmRNA表达水平没有影响,但VEGF蛋白的表达受到显著抑制。研究结果表明,力达霉素可以下调VEGF蛋白表达,从而抑制斑马鱼胚胎血管生成。Lidamycin （LDM） is a potent antitumor antibiotic. Previous studies have shown that LDM could inhibit proliferation and migration in endothelial cells. In the present report,the effect of LDM on angiogenesis of zebrafish embryo was studied. The results showed that treatment of zebrafish embryos with LDM resulted in significant inhibition of angiogenesis. Morphological observation,quantitative endogenous alkaline phosphatase （EAP） assay,alkaline phosphatase staining,and transgenic zebrafish assay were performed to evaluate vascular development defects in zebrafish. The results indicated that after the zebrafish embryos were exposed to LDM,angiogenesis defects of zebrafish embryos were observed,including pericardial edema,reduced numbers of circulating red blood cells,suppression of zebrafish vessel growth,and absences of SIV （subintestinal vein）. The expression of VEGF was detected by RT-PCR assay,quantitative reverse transcriptase real-time PCR （qRT-PCR） assay and Western blotting analysis. The results revealed that LDM could inhibit the expression of VEGF protein,while the expression of mRNA was not significantly affected. The study suggests that LDM could inhibit the zebrafish embryo angiogenesis by down-regulation of VEGF expression.

关 键 词：力达霉素 斑马鱼 血管生成 血管内皮生长因子 

分 类 号：R963[医药卫生—微生物与生化药学]