维甲酸受体与维甲酸致金黄地鼠神经管畸形的相关性研究

发布时间：2018-12-15 06:29

【摘要】：随着现代工业的发展和环境污染的日趋严重,人类先天性畸形发生率也逐年上升。因此对先天性畸形的研究已越来越受到人们的重视。神经管畸形(neuraltube defects,NTD)是最为常见,也是危害性最大的一类先天性畸形,因此探讨NTD形态发生机制已成为畸形学研究中一个非常活跃的领域。神经管的发生、分化和正常功能的建立受到诸多因素的影响和调控。这些调控因素一旦发生紊乱,就会出现各种形式的NTD。动物实验证实,多种致畸因子可以干扰哺乳动物神经管的形成过程,从而导致NTD,其中研究最多的是维生素A及其各种衍生物。研究证实,过量维生素A及维甲酸(retinoic acid,RA)等维生素A衍生物在小鼠、金黄地鼠、鸡等动物均可导致NTD。尽管人们从组织、细胞、亚细胞乃至分子水平上进行了广泛研究,但过量维生素A及其衍生物致NTD的确切机制至今仍不十分清楚。随着分子生物学技术的发展,现已证实,RA是胚胎发育过程中不可缺少的形态发生素,它不仅决定胚胎头尾轴的建立,而且参与在中枢神经系统发育过程中前、中、后脑和脊髓的分化;神经嵴细胞的迁移定位以及神经突起的定向生长等过程。在脑发育期间,它又是神经元分化的营养因子并且与神经损伤后的修复有关。关于RA的作用机制,目前主要倾向于受体学说。RA受体属于核内受体超家
[Abstract]:With the development of modern industry and environmental pollution, the incidence of human congenital malformation is increasing year by year. Therefore, more and more attention has been paid to the study of congenital malformation. Neural tube malformation (neuraltube defects,NTD) is one of the most common and harmful congenital deformities. Therefore, exploring the mechanism of NTD morphogenesis has become a very active field in the study of malformation. The occurrence, differentiation and establishment of normal function of neural tube are influenced and regulated by many factors. Once these regulatory factors are disturbed, there will be various forms of NTD.. Animal experiments have shown that many teratogenic factors can interfere with the formation of neural tubes in mammals, leading to the study of vitamin A and its derivatives in NTD,. It has been confirmed that excessive vitamin A and vitamin A derivatives such as retinoic acid (retinoic acid,RA) can cause NTD. in mice, golden hamsters, chickens and other animals. Although extensive studies have been carried out on tissue, cell, subcellular and even molecular levels, the exact mechanism of NTD induced by excessive vitamin A and its derivatives is still unclear. With the development of molecular biology technology, it has been proved that RA is an indispensable morphogenetic element in embryonic development, which not only determines the establishment of embryonic head and tail axis, but also participates in the process of central nervous system development. Differentiation of the posterior brain and spinal cord; Migration localization of neural crest cells and directional growth of neurites. During brain development, it is also a nutritional factor for neuronal differentiation and is associated with the repair of injured nerves. As to the mechanism of RA, the main tendency is the receptor theory. The RA receptor belongs to the nuclear receptor superfamily.
【学位授予单位】：山东大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R363

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