中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2020, Vol. 15 ›› Issue (4): 705-711.doi: 10.4103/1673-5374.266921

• 原著:神经损伤修复保护与再生 • 上一篇    下一篇

神经管缺陷胚胎神经管发育过程中白血病抑制因子受体蛋白的时空表达

  

  • 出版日期:2020-04-15 发布日期:2020-05-29
  • 基金资助:
    国家自然科学基金项目（81601292，81671469）；中国国家基础研究计划（973计划）（2013CB945402（ZWY）; 国家重点研究发展计划（2016YFC1000505）

Spatiotemporal expression of leukemia inhibitory factor receptor protein during neural tube development in embryos with neural tube defects

Dong An1, 2, Xiao-Wei Wei1, He-Nan Zhang1, Dan Liu1, Wei Ma1, Zheng-Wei Yuan1   

  1. 1 Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital, China Medical University, Shenyang, Liaoning Province, China
    2 Department of Pediatrics, The First Hospital of China Medical University, Shenyang, Liaoning Province, China
  • Online:2020-04-15 Published:2020-05-29
  • Contact: Zheng-Wei Yuan, MD,yuanzw@hotmail.com.
  • Supported by:
    This work was supported by the National Natural Science Foundation of China, No. 81601292 (to DA), No. 81671469 (to ZWY); the National Basic Research Program of China (973 Program), No. 2013CB945402 (to ZWY); the National Key Research and Development Program of China, No. 2016YFC1000505 (to ZWY).

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摘要：

白血病抑制因子受体作为神经调节因子受体，在中枢神经系统损伤病变中更多的是神经保护作用，为了解白血病抑制因子受体在神经管缺陷中发生中的作用，实验分析了不同胚胎发育期正常胚胎和神经管畸形胚胎脊髓组织白血病抑制因子受体的时空表达规律。应用维甲酸在大鼠神经管闭合的关键期(孕10 d，E10)给药，建立脊柱裂大鼠模型，观察孕11-17 d正常胎鼠和显性脊柱裂胎鼠白血病抑制因子受体时空表达情况，同时分别应用RT-PCR和Western-blot方法检测正常胚胎和神经管畸形胚胎脊髓组织白血病抑制因子受体mRNA及蛋白表达。(1)动物实验结果发现，白血病抑制因子受体蛋白及mRNA的表达在正常胎鼠脊髓组织中随胎龄的增长逐渐增加，白血病抑制因子受体水平在E11-E17脊柱裂组较正常组明显下调，免疫组织化学染色结果发现孕15 d在胎鼠脊髓和胎盘组织脊柱裂组白血病抑制因子受体蛋白的表达水平低于正常对照组；(2)人胚胎标本检测结果发现，在孕24-33周，神经管畸形胎儿组白血病抑制因子受体mRNA的表达水平明显低于相应正常对照组，其结果与上述动物实验结果下降趋势基本一致；(3)上述数据描述了在胚胎神经管发育时期白血病抑制因子受体的时空表达变化，白血病抑制因子受体可能在神经管发育时期扮演了特殊的作用。实验于2016-02-25经中国医科大学附属盛京医院医学伦理委员会批准，批准号：2016PS106K。

orcid: 0000-0002-6223-6612 (Zheng-Wei Yuan)

关键词: 神经管畸形, 显性脊柱裂, 脊髓, 血清, 羊水, 胎盘, 白血病抑制因子受体, 胚胎发生, 发育, 时空表达, 神经再生

Abstract: Leukemia inhibitory factor receptor (LIFR), as a neuroregulatory cytokine receptor, generally shows a neuroprotective effect in central nervous system injuries. In this study, to understand the effect of LIFR on pathogenesis of neural tube defects, we explored spatiotemporal expression of LIFR at different stages of fetal development in normal and neural tube defect embryos. Spina bifida aperta was induced with all-trans retinoic acid on embryonic day 10 in rats, and the spatiotemporal expression of LIFR was investigated in spina bifida aperta rats and healthy rats from embryonic day 11 to 17. Real time-polymerase chain reaction and western blot assay were used to examine mRNA and protein expression of LIFR in healthy control and neural tube defect embryos. Results of the animal experiment demonstrated that expression of LIFR protein and mRNA in the spinal cords of normal rat embryos increased with embryonic development. LIFR was significantly downregulated in the spinal cords of spina bifida aperta rats compared with healthy rats from embryonic days 11 to 17. Immunohistochemical staining showed that the expression of LIFR in placenta and spinal cord in spina bifida aperta rat embryos was decreased compared with that in control embryos at embryonic day 15. Results from human embryo specimens showed that LIFR mRNA expression was significantly down-regulated in spinal cords of human fetuses with neural tube defects compared with normal controls at a gestational age of 24 to 33 weeks. The results were consistent with the down-regulation of LIFR in the animal experiments. Our study revealed spatiotemporal changes in expression of LIFR during embryonic neurulation. Thus, LIFR might play a specific role in neural tube development. All animal and human experimental procedures were approved by the Medical Ethics Committee of Shengjing Hospital of China Medical University, China (approval No. 2016PS106K) on February 25, 2016.

Key words: amniotic fluid, development, embryogenesis, leukemia inhibitory factor receptor, nerve regeneration, neural tube defect, placenta, spatiotemporal expression, spina bifida aperta, spinal cord, serum