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 |
|
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) |
|
Hits: 841 |
Download times: 848 |
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. |
View Full Text
View/Add Comment Download reader |
Close |