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PMX诱导神经管畸形及其对神经上皮细胞增殖和凋亡的影响
引用本文:关涛,王秀伟,官臻,王建华,王国亮,朱智强,谢秋,牛勃. PMX诱导神经管畸形及其对神经上皮细胞增殖和凋亡的影响[J]. 神经解剖学杂志, 2011, 27(4): 447-452
作者姓名:关涛  王秀伟  官臻  王建华  王国亮  朱智强  谢秋  牛勃
作者单位:1. 山西医科大学生物化学与分子生物学教研室,太原,030001
2. 首都儿科研究所,北京,100020
摘    要:目的:用培美曲塞(pemetrexed,PMX)建立叶酸缺乏的神经管畸形(neural tube defect,NTD)动物模型,并探讨其对神经上皮细胞增殖和凋亡的影响。方法:应用不同剂量PMX(5、10、15、17.5、20和30 mg/kg)对C57BL/6孕鼠进行干预,筛选最佳造模剂量。采用磷酸化组蛋白H3(pH3免疫组化的方法以及TUNEL方法)观察胎鼠神经上皮增殖和凋亡情况。结果:随着PMX剂量的增加,小鼠胚胎的吸收胎和畸形率逐渐增加,其中17.5mg/kg体重组的NTD的发生率最高(30.6%),被筛选为最佳造模剂量。pH3免疫组化和TUNEL结果显示,与正常对照组相比,NTD小鼠胚胎神经上皮细胞增殖减少(P<0.05),凋亡增加(P<0.05)。结论:PMX能诱导NTD的发生,其机制可能是因为PMX阻断了叶酸代谢通路并导致神经上皮细胞的增殖抑制和过度凋亡。

关 键 词:培美曲塞  神经管畸形  细胞增殖  细胞凋亡  小鼠

Effect of PMX on the development of neural tube defects and neuroepithelial cell proliferation and apoptosis
Guan Tao,Wang Xiuwei,Guan Zhen,Wang Jianhua,Wang Guoliang,Zhu Zhiqiang,Xie Qiu,Niu Bo. Effect of PMX on the development of neural tube defects and neuroepithelial cell proliferation and apoptosis[J]. Chinese Journal of Neuroanatomy, 2011, 27(4): 447-452
Authors:Guan Tao  Wang Xiuwei  Guan Zhen  Wang Jianhua  Wang Guoliang  Zhu Zhiqiang  Xie Qiu  Niu Bo
Affiliation:Guan Tao1,Wang Xiuwei2,Guan Zhen2,Wang Jianhua2,Wang Guoliang2,Zhu Zhiqiang2,Xie Qiu2,Niu Bo2(1.Department of Biochemistry and Molecular Biology,Shanxi Medical University,Taiyuan 030001,2.Capital Institute of Pediatrics,Beijing 100020,China)
Abstract:Objective: To establish neural tube defect(NTD) animal model by pemetrexed(PMX) and explore the effects of PMX on neuroepithelial cell proliferation and apoptosis.Methods: To select an optimal dose,C57BL/6 pregnant mice were injected intraperitoneally with different doses of PMX(5,10,15,17.5,20,and 30 mg/kg body weight).TUNEL and immunohistochemisty method for phosphorylated histone H3(pH3) were used to detect neuroepithelial cell proliferation and apoptosis of NTD embryos.Results: With the increasing of PM...
Keywords:pemetrexed  neural tube defect  cellular proliferation  cellular apoptosis  mice  
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