摘要
流行病学研究显示,在胚胎发育过程中摄入过多维甲酸可致各种发育缺陷,其中神经管畸形最为常见. 因此有必要探明维甲酸致各种发育缺陷的发生机制,以便为各种生长缺陷的预防和治疗提供实验依据. 用 RT-PCR 及蛋白质印迹技术,探测了过量维甲酸对昆明小鼠胚胎神经管中维甲酸受体α/β及β-catenin 和 caspase-3 基因表达的调整. 结果显示,在神经管闭合期过量维甲酸显著降低了维甲酸受体α/β及β-catenin 和 caspase-3 的基因表达,神经管闭合后,维甲酸受体β、β-catenin 及 caspase-3 的基因表达又出现了一个明显的回升过程. 提示,过量维甲酸改变了昆明小鼠胚胎神经管中维甲酸受体α/β及β-catenin 和 caspase-3 基因的正常时间表达模式,这种异常的基因表达模式可能参与了维甲酸致昆明小鼠胚胎畸形的发生机制.
Epidemiologic studies suggest that intake of excess all-trans-retinoic acid （RA） during embryogenesis induces various developmental defects and the central nervous system （CNS） represents a major site of the teratogenic action of RA. It is therefore important to understand which parameters are affected early by excessive RA in order to devise and improve protective nutritional strategies. The modulations of beta-catenin and caspase-3 levels were investigated in the KM mouse embryo following maternal treatment with a single oral dose of 30mg/kg body weight of RA during the neurula period. In addition, retinoic receptors （RARs） arc key transcription factors regulating gene expression in response to RA-activated signals. So the experiment was designed to evaluate whether the alterations in protein expression of RAR alpha and beta during the time of neural tube closure were induced by excessive RA. Maternal intake of excess RA induced early downregulation of RAR alpha and beta, beta-catenin and caspase-3 expression, which was followed by an increase in their expressive levels in the neural tube tissue of mouse embryos. This finding suggests that the alterations in the expression profile of RAR alpha and beta, beta-catenin and caspasc-3 may be implicated in the teratogenesis induced by excess RA in KM mouse embryo.
出处
《生物化学与生物物理进展》
SCIE
CAS
CSCD
北大核心
2007年第11期1182-1189,共8页
Progress In Biochemistry and Biophysics
基金
山东省自然科学基金资助项目(Y2005C63).~~
