| 引用本文: | 高绪聪,孙程颖,张云,何秋霞,申秀萍.抗坏血酸联合全反式维甲酸建立斑马鱼新药早期评价模型的研究[J].中国现代应用药学,2018,35(12):1761-1764. |
| GAO Xucong,SUN Chengying,ZHANG Yun,HE Qiuxia,SHEN Xiuping.Zebrafish Model of New Drug Early Evaluation Established by Ascorbic Acid and All-trans Retinoic Acid[J].Chin J Mod Appl Pharm(中国现代应用药学),2018,35(12):1761-1764. |
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| 抗坏血酸联合全反式维甲酸建立斑马鱼新药早期评价模型的研究 |
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高绪聪1,2, 孙程颖1,2, 张云3, 何秋霞3, 申秀萍1,2
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1.天津药物研究院新药评价有限公司, 天津 300301;2.天津市新药非临床评价技术工程中心, 天津 300301;3.山东省科学院生物研究所, 济南 250014
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| 摘要: |
| 目的 以抗坏血酸和全反式维甲酸为工具药，建立斑马鱼药物早期评价模型，为药物毒性的早期筛查提供实验方法。方法 以斑马鱼胚胎培养用水为空白对照，二甲基亚砜为助溶剂，抗坏血酸为阴性药物，全反式维甲酸为阳性药物，对脱膜斑马鱼受精卵连续染毒5 d后，检测受精卵和幼鱼的死亡率，及幼鱼自由活动度、全身组织器官形态发育和骨骼发育情况。结果 0.5%二甲基亚砜和10 mg·L-1抗坏血酸对斑马鱼致死作用较弱，且无明显发育毒性作用，可分别用作常规助溶剂和质量控制标志药；全反式维甲酸随给药浓度升高，致畸效应加强，很好地呈现了自主活动缓慢到丧失、形态发育轻微异常到全身各组织器官严重畸形、骨骼矿化正常到抑制的全效应谱，为药物毒性的评价提供了很好的参照，其中7.5 μg·L-1可作为药物评价中阳性对照选用浓度。结论 用抗坏血酸和全反式维甲酸建立的斑马鱼模型设计合理，可用于药物毒性的早期评价。 |
| 关键词: 抗坏血酸 全反式维甲酸 斑马鱼 药物毒性检测 |
| DOI：10.13748/j.cnki.issn1007-7693.2018.12.002 |
| 分类号:R965.1 |
| 基金项目:国家科技重大专项（2015ZX09501004）；天津市科技计划项目（16PTGCCX00090） |
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| Zebrafish Model of New Drug Early Evaluation Established by Ascorbic Acid and All-trans Retinoic Acid |
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GAO Xucong1,2, SUN Chengying1,2, ZHANG Yun3, HE Qiuxia3, SHEN Xiuping1,2
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1.Tianjin Institute of Pharmaceutical Research New Drug Evaluation Co., Ltd., Tianjin 300301, China;2.Tianjin Engineering Research Center of Drug Preclinical Assessment Technology, Tianjin 300301, China;3.Shandong Province Biology Institute of Shandong Academy of Sciences, Jinan 250014, China
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| Abstract: |
| OBJECTIVE To establish a zebrafish model of drug early evaluation, using ascorbic acid and all-trans retinoic acid as tools, so as to provide a test method for early screening of drug toxicity. METHODS The zebrafish embryos were incubated for 5 days with water as the blank control, dimethyl sulfoxide as solvent, ascorbic acid(AA) as negative drug, all-trans retinoic acid(ATRA) as positive drug. Detected the mortality, movement, organs and skeleton morphogenesis of fertilized eggs and juveniles. RESULTS 0.5% DMSO and 10 mg·L-1 AA had weak lethal effect on zebrafish, and no obvious developmental toxicity, which could be used as cosolvent and quality control drug, respectively. ATRA had a strengthened teratogenic effect with the concentration increased, and showed a full-effect spectrum as follows:normal, slow and losed spontaneous activities, slight to severe tissues and organs malformations, vertebra mineralization inhibition. It provided a good reference for the evaluation of drug toxicity, and ATRA 7.5 μg·L-1 could be selected as the positive control drug evaluated concentration. CONCLUSION The zebrafish model designed with AA and ATRA reasonably can be used for early evaluation of drug toxicity. |
| Key words: ascorbic acid all-trans retinoic acid zebrafish drug evaluation |
