麦考酚酸对斑马鱼胚胎颅面部发育的影响

›› 2019, Vol. 39 ›› Issue (2): 103-107.

麦考酚酸对斑马鱼胚胎颅面部发育的影响

杨迷芳¹,马兰²,严冬琳³,⁴,蒋玲玲⁴

1. 江苏省口腔医院
2. 南京医科大学口腔医学院
3.
4. 南京医科大学附属口腔医院

收稿日期:2018-06-19 修回日期:2018-07-23 出版日期:2019-02-28 发布日期:2019-03-05
通讯作者: 蒋玲玲 E-mail:ling19910514@sohu.com

Effect of Mycophenolic acid on craniofacial development in zebrafish embryos

Received:2018-06-19 Revised:2018-07-23 Online:2019-02-28 Published:2019-03-05
Contact: Ling-Ling JIANG E-mail:ling19910514@sohu.com

摘要/Abstract

摘要： 目的　研究麦考酚酸对斑马鱼胚胎的颅面部发育毒性。方法：对斑马鱼胚胎进行麦考酚酸加药，观察不同时期麦考酚酸对胚胎造成的颅面部发育畸形。胚胎发育至72小时，软骨染色观察颅面部软骨的发育状况。Q-PCR方法检测次黄嘌呤核苷酸脱氢酶（IMPDH）基因的表达水平。同时鸟苷酸加药，从表型和基因层面考察鸟苷酸对麦考酚酸造成畸形的挽救情况。结果：麦考酚酸可以造成斑马鱼胚胎严重的颅面部畸形，染色结果显示颅面部软骨发育延迟，形态异常。基因检测发现麦考酚酸能够明显下调impdh1b和impdh2的表达水平。鸟苷酸可以挽救麦考酚酸造成的胚胎畸形。结论：麦考酚酸通过下调IMPDH基因，抑制了IMPDH活性，从而造成了斑马鱼胚胎的颅面部发育畸形。

关键词: 麦考酚酸, 颅面部发育, 斑马鱼, IMPDH通路

Abstract: Objective　 To explore the toxicity of Mycophenolic acid (MPA) on the craniofacial development of zebrafish embryos. Methods The zebrafish embryos were treated with MPA to observe the craniofacial malformation at different stages. In 72 hpf, cartilage staining was used to observe the development of craniofacial cartilage. Q-PCR was used to detect the expression level of IMPDH genes. The guanosine was added to examine its rescue of MPA-treated malformation in morphological and genetic aspects. Results MPA caused severe craniofacial malformation in zebrafish embryos. The staining results showed delayed craniofacial development and abnormal phenotype in treated embryos. Gene detection showed that the expression levels of impdh1b and impdh2 were significantly down-regulated by MPA acid. Guanosine could rescue malformation caused by MPA. Conclusion MPA can cause the craniofacial development malformation in zebrafish embryos by down-regulating the IMPDH genes which inhibits the activity of IMPDH.

Key words: Mycophenolic acid, craniofacial development, zebrafish, IMPDH pathway

中图分类号:

R722.23

杨迷芳马兰严冬琳蒋玲玲. 麦考酚酸对斑马鱼胚胎颅面部发育的影响[J]. , 2019, 39(2): 103-107.

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