| 季成 王秀伟 王建华 官臻 朱智强 谢秋 张霆 牛勃.甲氨蝶呤对早期神经胚基因表达的影响[J].,2014,14(26):5058-5062 |
| 甲氨蝶呤对早期神经胚基因表达的影响 |
| Alteration of Gene Expression by Methotrexate Exposure at EarlyNeurulation |
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| DOI： |
| 中文关键词: 神经管畸形 甲氨蝶呤 凋亡 增殖 |
| 英文关键词: Neural tube defects Methotrexate Apoptosis Proliferation |
| 基金项目: |
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| 中文摘要: |
| 摘要目的：利用甲氨蝶呤(methotrexate, MTX)干预孕鼠，探讨MTX对早期神经胚基因表达的影响。方法：用MTX（4.5 mg/kg 体
重）干预孕鼠，通过NimbleGene 表达谱芯片、Real time-PCR 及免疫组化等方法进行差异表达基因的筛选和验证。结果：MTX 处理
后神经管畸形（NTDs）发生率为32.1%。表达谱芯片筛选出166 个差异表达基因，其中4 个凋亡相关基因(Endog, Trp53, Casp3,
Bax) 均表现为上调(fold change >1.5，P<0.05)，3 个增殖相关基因(Ptch1, Pla2g4a, Foxg1)均表现为下调(fold change <0.67，P<0.05)；
NTDs 胚胎神经上皮Caspase-3 表达显著升高（P<0.05），phospho-histone H3（pH3）表达显著降低（P<0.05）。结论：MTX 影响了早期
神经胚的基因表达，尤其是引起了凋亡、增殖相关基因表达的异常，这可能在叶酸缺乏引起NTDs发生的相关机制之一。 |
| 英文摘要: |
| Objective:We used methotrexate (MTX) intervention in pregnant C57BL/6J mice to investigate the alteration of gene
expression at early neurulation. Methods:The differential gene expressions were studied by Microarray, RT-PCR and Immun
ohistochemical assays in NTD embryos induced by MTX（4.5 mg/kg body weight.Results:Results showed that 32.1% of NTDs was
developed by the treatment of MTX. Microarray indicated that 166 genes were significantly different between control and NTD mice,
including 4 apoptosis-related genes (Endog, Trp53, Casp3, Bax) and 3 proliferation-related genes (Ptch1, Pla2g4a, Foxg1). Levels of
Endog, Trp53, Casp3, Bax (fold change >1.5) were up-regulated but Ptch1, Pla2g4a, Foxg1 (fold change <0.67) were down-regulated
(P<0.05). Expression of caspase-3 was significantly enhanced (P<0.05) while phospho-histone H3 expression was markedly decreased
(P<0.05) in neuroepithelium from NTD embryos.Conclusion:MTX altered the gene expression at early neurulation, especially the
differential expression of apoptosis-and proliferation-related genes, which may be a critical mechanismin the occurrence of NTDs caused
by folate deficiency. |
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