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[1]董磊,杜勇,邓晓征,等.MTHFR、HCY与BDNF在大鼠胚胎神经管畸形发生中的作用[J].宁夏医科大学学报,2017,(11):1277-1280,1285.[doi:10.16050/j.cnki.issn1674-6309.2017.11.009]
 DONG Lei,DU Yong,DENG Xiaozheng,et al.The Roles of MTHFR,HCY and BDNF in the Development of Neural Tube Defects in Rat[J].Ningxia Medical University,2017,(11):1277-1280,1285.[doi:10.16050/j.cnki.issn1674-6309.2017.11.009]
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MTHFR、HCY与BDNF在大鼠胚胎神经管畸形发生中的作用(PDF)
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《宁夏医科大学学报》[ISSN:1005-8486/CN:64-1029/R]

卷:
期数:
2017年11期
页码:
1277-1280,1285
栏目:
论著
出版日期:
2017-11-30

文章信息/Info

Title:
The Roles of MTHFR,HCY and BDNF in the Development of Neural Tube Defects in Rat
作者:
董磊1杜勇2邓晓征1邢欣然2周瑜3
1.宁夏医科大学,银川 750004; 2.宁夏医科大学总医院小儿外科,银川 750004;  3.宁夏医科大学外科实验室,银川 750004
Author(s):
DONG Lei1DU Yong2DENG Xiaozheng1XING Xinran2ZHOU Yu3
1. Ningxia Medical University,Yinchuan 750004; 2. Department of Pediatric Surgery, the General Hospital of Ningxia Medical University,Yinchuan 750004; 3. Surgical Laboratory, Ningxia Medical University,Yinchuan 750004
关键词:
神经管畸形叶酸亚甲基四氢叶酸还原酶同型半胱氨酸脑源性神经营养因子
Keywords:
neural tube defectsfolic acidmethylenetetrahydrofolate reductasehomocysteine brain-derived neurotrophic factor
分类号:
R745.4
DOI:
10.16050/j.cnki.issn1674-6309.2017.11.009
文献标志码:
A
摘要:
目的 研究叶酸-同型半胱氨酸代谢途径中关键酶亚甲基四氢叶酸还原酶(methylenetetrahydrofolate reductase,MTHFR)、同型半胱氨酸( homocysteine,HCY)与脑源性神经营养因子(brain derived neurotrophic factor,BDNF)在大鼠神经管畸形发生中的作用。方法 将30只成年雌性SD大鼠随机分为正常对照 组(正常组)、神经管畸形组(畸形组)、叶酸干预组(叶酸组),每组各10只。于孕鼠妊娠第15.5天时,采用 酶联免疫吸附法(ELISA)测定孕鼠血浆HCY浓度;取大鼠胚胎,免疫组织化学染色分析胚胎神经管组织MTHFR、 BDNF表达量、TUNEL染色(过氧化物酶标记测定法)分析胚胎神经管组织细胞凋亡率。结果 与正常组相比,畸形 组孕鼠血浆HCY浓度升高(P<0.05),胚胎神经管组织中MTHFR、BDNF因子的免疫组织化学染色平均光密度(MOD )值下降 (P<0.05),TUNEL染色显示胚胎神经管组织中细胞凋亡率升高(P<0.05),叶酸组孕鼠血浆HCY浓度 无明显变化(P>0.05),胚胎神经管组织中MTHFR、BDNF的免疫组化染色MOD值下降(P<0.05),TUNEL染色显示 胚胎神经管组织神经细胞凋亡率无明显变化(P>0.05)。与畸形组比,叶酸组孕鼠血浆 Hcy浓度降低(P<0.05 ),胚胎神经管组织中MTHFR、BDNF因子的MOD值升高(P<0.05),TUNEL染色显示神经细胞凋亡率降低(P<0.05 )。结论 胚胎神经管组织发育中MTHFR表达降低致HCY蓄积,引起BDNF表达下调,细胞凋亡增加,从而导致神经管 关闭受阻;叶酸补充后较好地逆转这一过程,从而预防大部分神经管畸形的发生。
Abstract:
Objective To study the role of folate homocysteine metabolism key enzyme methylenet- etrahydrofolate reductase(MTHFR),homocysteine(HCY) and brain-derived neurotrophic factor (BDNF) in the rat neural tube defects pathogenesised. Methods A total of 30 adult female SD rats were randomly divided into normal group,all-transretinoic acid(ATRA) group and folic acid treatment group,with 10 rats in each group. HCY concentration in plasma of pregnant rats on E15.5d of gestation was determined by ELASA. The expression of MTHFR and BDNF in E15.5d embryonic neural tube tissue was examed by using immunohistochemistry analysis. The embryonic neural tube tissue cell apoptosis was checked by TUNEL staining. Results Compared with the normal group,HCY concentration increased in deformity of pregnant rats plasma(P<0.05). Mean optical density(MOD) value of immunohistochemical staining for MTHFR,BDNF factor in embryonic neural tube defect tissue decreased(P<0.05). TUNEL staining showed that the cell apoptosis increased in embryonic neural tube defect tissue(P<0.05). Adding folic acid treatment group in plasma HCY concentration of pregnant rats had no significant change(P>0.05). MOD of MTHFR and BDNF in embryonic neural tube tissue decreased (P<0.05). TUNEL staining showed no obvious changes of embryonic nerve tube nerve cell apoptosis(P >0.05). Compared with the neural tube defect group,in folic acid treatment group,Hcy plasma concentration of pregnant rats decreased (P<0.05),MOD of MTHFR, BDNF increased in the embryonic neural tube tissue and the apoptosis of neural cells reduced (P<0.05). Conclusion The decreased expression of MTHFR in neural tube defects rats induced HCY accumulation in the tissue of neural tube tissue,decreased the expression of BDNF and increased apoptosis of embryonic neural cells,which led to defects in the closure of neural tube tissue. Folic acid can inhibit the process,so as to effectively prevent the most of pathogenesis in neural tube defects.

参考文献/References:

[1] Agunath PK,Abhinand PA. Systems biological approach to investigate the lack of familial link between Down's Syndrome & Neural Tube Disorders[J]. Bioinformation,2013,9(12):610-616.
[2] 陈晓丽,郭 金,邹继珍,等. DNA 总体低甲基化、错配修复基因启动子甲基化异常与神经管畸形的相关性[J]. 中国循证儿科杂志,2012,7(2):102-106.
[3] 张克明,黄国伟. 叶酸、维生素B12、B6与同型半胱氨酸代谢及脑卒中关系的研究新进展[J]. 医学理论与实践,2013,26(5):585-587.
[4] Melo CV,Okumoto S,Gomes JR,et al. Spatiotemporal resolution of BDNF neuroprotection against glutamate excitotoxicity in cultured hippocampal neurons[J]. Neuroscience,2013,237(6):66.
[5] Fischer M,Stronati M,Lanari M. Mediterranean diet,folic acid,and neural tube defects:[J]. Italian Journal of Pediatrics,2017,43(1):34-38.
[6] Noor RA,Abioye AI,Ulenga N,et al. Large -scale wheat flour folic acid fortification program increases plasma folate levels among women of reproductive age in urban Tanzania[J]. Plos One,2017,12(8):e0182099.
[7] Yan L,Zhao L,Long Y,et al. Association of the maternal MTHFR C677T polymorphism with susceptibility to neural tube defects in offsprings: Evidence from 25 case-control studies[J]. Plos One,2012,7(10):e41689.
[8] Reilly R,Mcnulty H,Pentieva K,et al. MTHFR 677TT genotype and disease risk: is there a modulating role for B-vitamins[J]. Proceedings of the Nutrition Society,2014,73(1):47.
[9] Gao L,Liu X,Yu L,et al. Folic acid exerts antidepressant effects by upregulating brain-derived neurotrophic factor and glutamate receptor 1 expression in brain[J]. Neuroreport,2017,75(8):32-36.
[10] Kobusbianchini K,Bourckhardt GF,Ammar D,et al. Homocysteine-induced changes in cell proliferation and differentiation in the chick embryo spinal cord: implications for mechanisms of neural tube defects (NTD)[J]. Reproductive Toxicology,2017,69:167-173.
[11] Hai-jun,Jin-hua,Man-hong,et al. Hydrogen sulfide inhibits homocysteine-induced endoplasmic reticulum stress and neuronal apoptosis in rat hippocampus via upregulation of the BDNF-TrkB pathway[J]. Acta Pharmacologica Sinica,2014,35(6):707-715.
[12] Zhang C,Shen L. Folic acid in combination with adult neural stem cells for the treatment of spinal cord injury in rats[J]. International Journal of Clinical & Experimental Medicine,2014,8(7):10471-10480.

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备注/Memo

备注/Memo:
收稿日期:2017-07-03
基金项目:国家自然科学基金(81260100)
作者简介:董磊(1984-),女,在读硕士研究生,研究方向:神经管畸形。
通信作者:杜勇,博士,主任医师,研究方向:神经管畸形的发生机制。E-mail:niniduy@126.com
更新日期/Last Update: 1900-01-01