药学学报, 2010, 45(4): 456-461
引用本文:
丁丽丽 刘 明 张胜华 赵向忠 吴 宁 陈 雷 王广建 林秀坤. 力达霉素通过下调VEGF表达抑制斑马鱼胚胎血管生成[J]. 药学学报, 2010, 45(4): 456-461.
DING Li-Li, Liu- Meng, Zhang-Qing-Hua, Diao-Xiang-Zhong, Tun- Ning, Chen- Lei, Wang-An-Jian, Lin-Xiu-Kun. Lidamycin inhibits angiogenesis of zebrafish embryo via down-regulation of VEGF[J]. Acta Pharmaceutica Sinica, 2010, 45(4): 456-461.

力达霉素通过下调VEGF表达抑制斑马鱼胚胎血管生成
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*
(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)
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VEGF mRNA表达水平没有影响, 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。

关键词:   
Lidamycin inhibits angiogenesis of zebrafish embryo via down-regulation of VEGF
Abstract:

 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.

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