摘要
目的:考察甘脯酰阿霉素(Z-GP-Dox)对斑马鱼胚胎的急性毒性、心脏毒性及外周血液毒性。方法:以24hpf(受精后小时)斑马鱼胚胎为模型,二甲基亚砜(DMSO)为溶剂,以1.25、2.5、5、10、15、20μmol·L-1Z-GP-Dox与阿霉素(Dox)对48、72、96hpf胚胎存活率的影响考察急性毒性,以5、10μmol·L-1Z-GP-Dox与Dox对72hpf胚胎心率的影响考察心脏毒性,以对红细胞和嗜中性细胞数量的影响考察外周血液毒性,并设溶剂对照组进行比较。结果:溶剂对胚胎存活无明显影响,Dox>10μmol·L-1时,96hpf胚胎存活率小于25%,而Z-GP-Dox为20μmol·L-1时依然有70%以上的胚胎存活;与溶剂对照组比较,5、10μmol·L-1Dox明显降低胚胎的心率和嗜中性细胞数量,而5、10μmol·L-1Z-GP-Dox对胚胎心率、红细胞和嗜中性细胞数量均无明显影响。结论:Z-GP-Dox的毒性比Dox低。
OBJECTIVE： To investigate the acute toxicity, cardiotoxicity and peripheral blood toxicity of N-carbobenzoxy-gly- cyl-proline-Dox （Z-GP-Dox） to zebrafish embryos. METHODS： With 24 hpf （duration after fertilization） zebrafish embryos as model and DMSO as solvent, the effets of 1.25, 2.5, 5, 10, 15 and 20 μmol,L-1 Z-GP-Dox and Dox on survival rate of 48, 72 and 96 hpf embryos were investiagted to study acute toxicity; of 72 hpf embryos were investiagted to study cardiotoxicity; the effects of 5 and 10 μmol-L-1 Z-GP-Dox and Dox on survival rate the effects of Z-GP-Dox and Dox on the distribution and the number of red blood cell and neutrophil cell were investiagted to study peripheral blood toxicity, compared with solvent control group. RE- SULTS： Solvent had no significant effect on embryos survival. Less than 25% embryos were alive after 96 hpf when Dox〉10 μ mol.L-1, while more than 70% embryos were suvival at 20 μmol.L-1 Z-GP-Dox. Compared with solvent control group, 5 and 10 μ mol.L-1 Dox could reduce heart rate and the number of neutrophil cell; 5 and 10 μmol.L-1Z-GP-Dox had no significant effect on reducing heart rate and the number of red blood cell and neutrophil cell. CONCLUSION： The toxicity of Z-GP-Dox is significantly lower than that of Dox.
出处
《中国药房》
CAS
CSCD
2012年第41期3882-3884,共3页
China Pharmacy
作者简介
赵海山,硕士研究生。研究方向:药理学。电话:020-88467707。E-mail:lordharrt_39@163.com;通讯作者:蔡绍晖,教授,博士。研究方向:分子药理学。E-mail:csh5689@sina.com
