Department of Pediatric Surgery, Shengjing Hospital of China Medical University, Weilin Wang. 36, Sanhao Street, Heping District, Shenyang, 110004, Liaoning, China.
J Mol Histol. 2020 Oct;51(5):519-530. doi: 10.1007/s10735-020-09900-w. Epub 2020 Aug 11.
Complications, such as fecal soiling, incontinence, and constipation, are major health issues for patients with anorectal malformations (ARMs) after surgery. Dysplasia of the caudal spinal cord is an increasingly pivotal area in the field of postoperative complications for patients with ARMs. However, the existing research has not fully defined the mechanism underlying ARMs development. The neurogenic locus notch homolog (Notch) signaling pathway comprises several highly conserved proteins that are involved in spinal cord developmental processes. In the present study, the emerging role of Notch1 in fetal lumbosacral spinal cords was investigated in a rat model of ARMs using ethylene thiourea. Immunohistochemical staining, western blot and quantitative reverse transcription real-time polymerase chain reaction were utilized to analyze spatiotemporal expression of Notch1 on embryonic days (E) 16, E17, E19, and E21. The expression levels of the neuronal marker neurofilament and recombination signal-binding protein-J protein were evaluated for temporal correlations to Notch1 expression. The results implied that Notch1 expression was reduced in lumbosacral spinal cord neurons of ARMs embryos compared to control embryos. These results showed that, in ARMs embryos decreased Notch1 expression is related to the dysplasia of the caudal spinal cord during embryogenesis, indicating that Notch signaling may participate pathogenic embryonic lumbosacral spinal development and may be associated with postoperative complications of ARMs.
并发症,如粪便污染、失禁和便秘,是肛门直肠畸形(ARM)患者手术后的主要健康问题。尾部脊髓发育不良是 ARM 患者术后并发症领域中一个日益重要的领域。然而,现有研究尚未完全定义 ARM 发展的机制。神经源性同源框(Notch)信号通路包含几个高度保守的蛋白质,它们参与脊髓发育过程。在本研究中,使用乙撑硫脲在 ARM 大鼠模型中研究了 Notch1 在胎儿腰骶脊髓中的新作用。免疫组织化学染色、western blot 和定量逆转录实时聚合酶链反应用于分析 Notch1 在胚胎第 16、17、19 和 21 天(E)的时空表达。评估神经元标记物神经丝和重组信号结合蛋白-J 蛋白的表达水平与 Notch1 表达的时间相关性。结果表明,与对照胚胎相比,ARM 胚胎腰骶脊髓神经元中的 Notch1 表达减少。这些结果表明,在 ARM 胚胎中,Notch1 表达减少与胚胎发生过程中尾部脊髓的发育不良有关,表明 Notch 信号可能参与致病性胚胎腰骶脊髓发育,并可能与 ARM 的术后并发症有关。