| 徐文婧 关涛 王建华 季成 董艳婷 周楠 张霆 牛勃.MTX诱导神经管畸形动物模型的建立[J].现代生物医学进展英文版,2014,14(25):4837-4842. |
| MTX诱导神经管畸形动物模型的建立 |
| The Establishment of Folate Deficiency-related Animol Model of NeuralTube Defects by MTX |
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| DOI： |
| 中文关键词: 神经管畸形 甲氨蝶呤 叶酸缺乏 |
| 英文关键词: Neural tube defects Methotrexate Folate deficiency |
| 基金项目:国家自然科学基金项目（81070491） |
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| 中文摘要: |
| 目的：通过二氢叶酸还原酶（DHFR）竞争性抑制剂甲氨蝶呤（MTX）建立叶酸缺乏的神经管畸形（NTDs）动物模型。方法：本
研究用孕7.5 天C57BL/6J 小鼠，采用腹腔注射（ip）不同剂量的MTX 建立叶酸代谢障碍的小鼠NTDs 模型，LC / MS / MS 及酶学
方法检测胚胎组织中叶酸相关代谢产物水平及DHFR 活性。结果：最佳的致畸剂量为，MTX 4.5 mg/kg，其NTDs 发生率最高为
31.4 %。畸形的胎鼠表型多数为后脑泡未闭，且其身长（4.21± 0.76），体重（9.49± 3.48）均明显低于对照组（6.32± 0.56；22.76±
3.23）（P<0.05；P<0.05）。MTX 实验组的胚胎组织中DHFR 的活性较对照组显著降低（P<0.05），5-MeTHF 和5-FoTHF 的浓度和对
照组相比也明显降低（P<0.05）。结论：本研究成功的建立了叶酸缺乏的神经管畸形动物模型。 |
| 英文摘要: |
| Objective:To establish the animal model of neural tube defects (NTDs) by folate deficiency induced dihydrofolate
reductase (DHFR) inhibitor, methotrexate (MTX).Methods:The NTDs animal model was established by intraperitoneal injection of
different doses of MTX into pregnant C57BL/6J mice on gestational day 7.5. Folate-related metabolic products and DHFR activity in
embryo tissues were measured by using LC/MS /MS assay.Results:MTX with the dose of 4.5 mg/kg induced the highest incidence of
NTDs (31.4%) and was considered as the optimal teratogenic dosage. Most NTDs exhibited the failure of hindbrain closure of the neural
tube and the body length (4.21± 0.76) and weight (9.49± 3.48) decreased significantly compared with that in the control group(6.32±
0.56 vs 22.76± 3.23), (P<0.05 vs P<0.05). DHFR activity and concentrations of 5-MeTHF and 5-FoTHF were obviously lower than that
in the control group after MTX treatment (P<0.05).Conclusion:animal model induced by folate deficiency was successfully
established. |
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