山东科学 ›› 2015, Vol. 28 ›› Issue (5): 14-21.doi: 10.3976/j.issn.1002-4026.2015.05.003

• 药理与毒理 • 上一篇    下一篇

异烟肼对斑马鱼胚胎发育量-毒关系的研究

张云1,吴媛2,陈维云1,孙晨1,王希敏1,何秋霞1,韩利文1,王雪1,韩建1,刘可春1*   

  1. 1.山东省科学院生物研究所,山东省生物传感器重点实验室,山东 济南 250014; 2.山东省职业卫生与职业病防治研究院,山东 济南 250062
  • 收稿日期:2015-06-01 出版日期:2015-10-20 发布日期:2015-10-20
  • 通信作者: 刘可春 E-mail:hliukch@sdas.org
  • 作者简介:张云(1982-),女,博士,研究方向为药物筛选和药物分子毒理学。Email:xiaohan_0818@163com
  • 基金资助:
    山东省自主创新重大专项(2014ZZCX0215);山东省科学院青年科学基金项目(2013QN001);山东省自然科学基金三院联合基金(ZR2015YL010)

Dosedependent developmental toxicity of isoniazid to zebrafish embryo

ZHANG Yun1, WU Yuan2, CHEN Weiyun1,SUN Chen1,WANG Ximin1,HE Qiuxia1, HAN Liwen1,WANG Xue1,HAN Jian1, LIU Kechun1*   

  1. 1.Shandong Provincial Key Laboratory of Biosensors, Biology Institute, Shandong Academy of Sciences, Jinan 250014, China; 2.Shandong Academy of Occupational Health and Occupational Medicine, Jinan 250062, China
  • Received:2015-06-01 Online:2015-10-20 Published:2015-10-20

摘要: 研究了一线抗结核药物异烟肼对斑马鱼发育的量-毒关系。用不同浓度的异烟肼分别处理发育至2 hpf(hour post fertilization)的斑马鱼胚胎,观察胚胎和幼鱼的死亡率、孵化率、畸形率、体长及形态学变化。急性毒性实验结果表明异烟肼对斑马鱼有明显的发育毒性,能导致斑马鱼发育迟缓和畸变。与对照组相比,低剂量(小于6 mmol/L)异烟肼对斑马鱼无发育毒性,高剂量(≥32 mmol/L)异烟肼显著抑制胚胎的孵化率,并有明显的胚胎致死效应和致畸效应。斑马鱼死亡率和畸形率均随给药剂量的增加和给药时间的延长而升高。本实验条件下,异烟肼的最大无毒性效应浓度为2 mmol/L。

关键词: 斑马鱼, 发育毒性, 异烟肼

Abstract: We address dosedependent developmental toxicity of isoniazid (INH) to zebrafish. We respectively process 2hpf zebrafish embryo with different concentrations of INH, and observe the variations of the mortality of zebrafish larva and embryo, hatching rate, malformation rate, body length and morphology. Acute toxicity experiment shows that INH has significant developmental toxicity to zebrafish, and can cause developmental delay and malfunction of zebrafish. Compared with the control group, lower doses (<6 mmol/L) of INH have no developmental toxicity to zebrafish, while higher doses (≥32 mmol/L) of INH significantly inhibit hatching rate of embryos, and have obvious embryonic death and teratogenic effects. Mortality and malformation rates of zebrafish both increase with the increase of drug delivery dosage and time extension. For this experiment, the largest concentration of INH nontoxic effect is 2 mmol/L.

Key words: isoniazid, zebrafish, developmental toxicity

中图分类号: 

  • R996.3