摘要
目的利用叶酸相关代谢关键酶抑制剂5-氟尿嘧啶干预孕鼠(C57 BL/6J),探讨5-氟尿嘧啶对早期胚胎神经发育的影响。方法用12.5mg/kg体重的5-氟尿嘧啶,在胚胎神经管发育开始干预孕鼠,体视镜及苏木精-伊红(HE)染色光学显微镜下观察子代活胎数、死胎数、畸形胎数及神经管发育的情况,通过western blot及real time-qPCR方法观察5-氟尿嘧啶对早期神经发育中细胞增殖、凋亡的影响。结果 12.5mg/kg体重5-氟尿嘧啶处理后的神经管畸形的发生率为40.68%,HE染色可见畸形胎鼠端脑和后脑结构紊乱,增殖相关基因增殖细胞核抗原(Pcna)的表达水平明显降低,而凋亡相关基因Caspase3的表达明显增高(P<0.05)。结论 5-氟尿嘧通过啶影响了早期胚胎神经管发育过程中增殖、凋亡相关基因的表达,这可能是神经管畸形发生的相关机制之一。
Objective:To investigate the effect on early embryonic neural development by using the 5-fluorouracil intervention in pregnant C57BL/6J mice.Methods:12.5mg/kg 5-fluorouracil was used to intervene the pregnant mice on early embryonic neural development.The embryos were carefully observed with steromicroscope.The number of embryos and malformation rates were recorded.Neural tube closure was examined by hematoxylin-eosin(HE)staining under optical microscope.Western blot and real time-qPCR were used to detect the proliferation and apoptosis at early embryonic neural development.Results:The incidence of neural tube defects(NTDs)were 40.68% after 12.5mg/kg 5-fluorouracil treatment.The results of HE staining showed that the structure of telencephalon and fourth ventricle were abnormal.Expressions of proliferating cell nuclear antigen(Pcna)were significantly decreased in the NTD group,while apoptosis related gene Caspase3/Casp3 were significantly increased in the NTD group compared with the control group(P<0.05).Conclusion:These results indicated that 5-fluorouracil affected the early embryonic neural development via altered the expression of proliferation and apoptosis related genes or protein,which might shed some lights on the mechanisms involved in NTDs.
作者
王秀伟
官臻
朱智强
牛勃
王建华
WANG Xiu-wei;GUAN Zhen;ZHU Zhi-qiang;NIU Bo;WANG Jian-hua(Beijing Municipal Key Laboratory of Child Development and Nutriomics,Capital Institute of Pediatrics,Beijing,100020,China)
出处
《中国优生与遗传杂志》
2020年第2期239-242,共4页
Chinese Journal of Birth Health & Heredity
基金
国家自然科学基金项目(81600984,81571443,81700777)
北京市自然基金(7172038)
首都儿科研究所所级基金(FX-2018-05)。
关键词
神经管畸形
5-氟尿嘧啶
小鼠
增殖
叶酸
Neural tube defects
5-fluorouracil
Mice
Proliferation
Folic acid
