Notch-1及Jagged-2基因在肛门直肠畸形大鼠直肠发育过程中的表达及意义

Notch-1 and Jagged-2 Expression during Rectum Development in the Anorectal Unit of Fetal Rats with Ethylenethiourea Induced Anorectal Malformations

目的检测Notch-1及Jagged-2基因在肛门直肠畸形(ARM)胎鼠直肠肠壁的胚胎发育过程中的表达变化,探讨其与肠壁神经肌肉发育的关系。方法应用免疫组化和Western blot方法检测正常与乙烯硫脲致畸的ARM胎鼠直肠末端组织Notch-1及Jagged-2蛋白的定位及定量表达,应用RT-PCR方法检测Notch-1及Jagged-2基因mRNA的表达差异。结果 Notch-1/Jagged-2在正常大鼠胚胎直肠发育过程中,在肠壁肌间神经丛(MP)、肠壁平滑肌及黏膜层均有表达,随着胚胎发育,表达强度逐渐增强,胚胎晚期主要集中在肠壁平滑肌及神经丛处;ARM组E17～E21表达均较正常组减弱,E19～E21表达与正常组差异更为显著。正常胎鼠直肠末端壁内中Notch-1及Jagged-2总蛋白量及mRNA明显高于畸形组(P<0.05)。结论 Notch-1/Jagged-2基因在肛门直肠畸形的神经肌肉发育过程中表达下调,可能与其发育不良有一定关系。

Objective To explore the role of Notch-1 and Jagged-2 genes expression during the neuromuscular development of normal and anorectal malformations （ARM） rat embryos.Methods The expression of Notch-1 and Jagged-2 in the anorectal unit of normal and ethylenethiourea（ETU）induced ARM rat embryos was detected by immunohistochemical staining,reverse transcription polymerase chain reaction（RT-PCR）and Western blot.Results In the normal control group,Notch-1 and Jagged-2 expression were observed in the myenteric nerve plexus （MP）,smooth muscle layers and the mucosa of the rectum;the expression levels increased time-dependently;the expression mainly confined to the MP and smooth muscle layers in the late phase.In ARM embryos on embryonic day 17 to 21 （E17-21）,the expression levels showed time-dependent changes and were lower than those of the normal contro（lP 〈 0.05）.Conclusion In ARM embryos,the downregulated expression of Notch-1 and Jagged-2 during the neuromuscular development might be related to the neuromuscular maldevelopment.