CAJ | 학술논문

背景:目前斑马鱼胚胎毒性试验在国内已广泛应用于环境、农业和生态学领域,但其在药物毒性筛选的应用仍处于起步阶段. 目的:运用斑马鱼胚胎试验比较4种常用抗肿瘤药物注射剂的毒性强弱,评估斑马鱼胚胎试验用于药物毒性筛选的效果. 方法:挑选6 hpf时发育正常的受精卵进行药物暴露.环磷酰胺、盐酸阿糖胞苷、氟尿嘧啶、硫酸长春新碱4种待测药物分别设置7个实验组,包括:5个药物浓度组,空白对照组(Holt Buffer溶液),助溶剂对照组(含0.5%二甲基亚砜的Holt Buffer溶液).于72 hpf观察斑马鱼胚胎的发育变化,并统计各实验组斑马鱼胚胎的死亡数、孵化数、畸形数以及各种发育缺陷,并据此求取在72 hpf时,斑马鱼胚胎畸形率、死亡率、各药物毒力方程、相关系数和95%置信限及LD50、ED50和LD1/ED99. 结果与结论:斑马鱼胚胎试验中,测得4种常见抗肿瘤药物注射剂 LD50从大到小依次排序为:环磷酰胺>盐酸阿糖胞苷>氟尿嘧啶>硫酸长春新碱.ED50由大到小依次排序为:环磷酰胺>盐酸阿糖胞苷>氟尿嘧啶>硫酸长春新碱.LD1/ED99由大到小依次排序为:硫酸长春新碱>氟尿嘧啶>环磷酰胺>盐酸阿糖胞苷.结果表明,斑马鱼胚胎试验方法可适用于快速有效测试多种药物的毒性及评价药物安全性,达到高通量筛选药物的目的.
배경:목전반마어배태독성시험재국내이엄범응용우배경、농업화생태학영역,단기재약물독성사선적응용잉처우기보계단. 목적:운용반마어배태시험비교4충상용항종류약물주사제적독성강약,평고반마어배태시험용우약물독성사선적효과. 방법:도선6 hpf시발육정상적수정란진행약물폭로.배린선알、염산아당포감、불뇨밀정、류산장춘신감4충대측약물분별설치7개실험조,포괄:5개약물농도조,공백대조조(Holt Buffer용액),조용제대조조(함0.5%이갑기아풍적Holt Buffer용액).우72 hpf관찰반마어배태적발육변화,병통계각실험조반마어배태적사망수、부화수、기형수이급각충발육결함,병거차구취재72 hpf시,반마어배태기형솔、사망솔、각약물독력방정、상관계수화95%치신한급LD50、ED50화LD1/ED99. 결과여결론:반마어배태시험중,측득4충상견항종류약물주사제 LD50종대도소의차배서위:배린선알>염산아당포감>불뇨밀정>류산장춘신감.ED50유대도소의차배서위:배린선알>염산아당포감>불뇨밀정>류산장춘신감.LD1/ED99유대도소의차배서위:류산장춘신감>불뇨밀정>배린선알>염산아당포감.결과표명,반마어배태시험방법가괄용우쾌속유효측시다충약물적독성급평개약물안전성,체도고통량사선약물적목적.
BACKGROUND:Zebrafish embryo toxicity test in China has been widely used in the field of environment, agriculture and ecology, but for the toxicity of drugs, it is stil in its infancy. @@@@OBJECTIVE:To compare the toxicity of four common anti-cancer drug injections through zebrafish embryo test to further evaluate the potential of zebrafish embryo test for drug toxicity screening. @@@@METHODS:Normal developed fertilized 6 hours post-fertilization eggs were selected for drug exposure. The cyclophosphamide, cytarabine hydrochloride, fluorouracil and vincristine sulfate were divided randomly into seven groups, including five test groups treated with different drug-concentrations, blank control group (Holt Buffer, Control A) and cosolvent control group (Holt Buffer contained 0.05%dimethyl sulfoxide, Control B). The development of zebrafish embryos were observed at 72 hours post-fertilization, and the death number, hatching number, malformation and other development defects were al recorded. The malformation rate, mortality rate, regression equation, correlation coefficient and 95%confidence limits, LD50, ED50, and LD1/ED99 were calculated accordingly at 72 hours post-fertilization. @@@@RESULTS AND CONCLUSION:The results from zebrafish embryo test showed that LD50 of the four drugs ranged from high to low:cyclophosphamide>cytarabine hydrochloride>fluorouracil>vincristine sulphate. ED50 ranged from high to low:cyclophosphamide>cytarabine hydrochloride>fluorouracil>vincristine sulphate. LD1/ED99 ranged from high to low:vincristine sulphate>fluorouracil>cyclophosphamide>cytarabine hydrochloride. Comparison of toxicity of four anti-cancer drugs in zebrafish embryo test suggests that the zebrafish embryo test is suitable for fast-screening and accessing drug toxicity and safety for several drugs, which can be used for high-throughput drug screen.