高温致畸金黄地鼠胚胎神经管cDNA文库的构建及致畸相关基因的筛查

发布时间：2019-06-28 17:33

【摘要】：在脊椎动物胚胎发育过程中，神经胚是一个重要的发育时期。这个阶段胚胎外胚层增厚形成上皮性神经板，神经板两侧隆起形成神经褶，随后神经褶两侧向背中线靠拢并愈合成神经管。神经管的发生和分化是脑和脊髓正常发育的前提，这一发育过程发生异常就会导致神经管畸形(neural tube defects，NTDs)。随着现代工业的发展和环境污染的日趋严重，人类先天畸形的发生率也逐年上升。1986年调查结果显示，我国新生儿先天畸形的发生率高达1.3％，因此，对先天畸形的研究越来越受到人们的重视。在各类先天畸形中，神经管畸形是发生率最高、危害也最为严重的一类先天畸形，由胚胎发育早期神经管闭合不全或延迟闭合所致，主要涉及中枢神经系统，包括无脑、露脑、脊柱裂等。神经管畸形也是导致死胎、流产和早产的主要原因之一，其致残率很高，给家庭和社会带来严重的心理和经济负担。NTDs的病因非常复杂，既有遗传因素，也有环境因素，更包含着遗传因素与环境因素之间的交互作用。流行病学调查及动物实验显示，高温是最常见且难以预防的一种物理致畸因子，，可引起多种动物以及人类的先天畸形，其中以NTDs的出现率最高。近年来，各国学者在高温致畸方面作了大量的动物实验和细胞培养研究，观察了高温对细胞增殖、细胞凋亡、细胞分化、细胞粘着、细胞类聚、组织诱导和器官发生等方面的影响，取得了不少成果，但至今仍未阐明高温致畸的分子机理。高温致NTDs是一个极其复杂的过程，在这个过程中，有些蛋白质的合成，尤其是与胚胎分化
[Abstract]:In the process of vertebrate embryo development, neuroembryo is an important developmental period. At this stage, the ectoderm thickens to form an epithelial nerve plate, which forms a nerve fold on both sides of the nerve plate, and then the two sides of the nerve fold approach the dorsal midline and heal into a neural tube. The occurrence and differentiation of neural tube is the premise of normal development of brain and spinal cord, which will lead to neural tube malformation (neural tube defects,NTDs). With the development of modern industry and the increasingly serious environmental pollution, the incidence of congenital malformations in human beings is also increasing year by year. The results of 1986 survey show that the incidence of congenital malformations in China is as high as 1.3%. Therefore, more and more attention has been paid to the study of congenital malformations. Among all kinds of congenital malformations, neural tube malformation is the highest incidence and the most serious congenital malformation, which is caused by incomplete or delayed closure of neural tube in the early stage of embryonic development, mainly involving the central nervous system, including anencephalia, open brain, spina bifida and so on. Neural tube malformation is also one of the main causes of stillbirth, abortion and premature delivery, and its disability rate is very high, which brings serious psychological and economic burden to family and society. The etiology of NTDs is very complex, there are both genetic and environmental factors, but also contains the interaction between genetic factors and environmental factors. Epidemiological investigation and animal experiments show that high temperature is the most common and difficult to prevent physical teratogenic factors, which can cause congenital malformations in many animals and humans, among which NTDs has the highest occurrence rate. In recent years, scholars from all over the world have done a lot of animal experiments and cell culture studies on high temperature teratogenesis. The effects of high temperature on cell proliferation, apoptosis, cell differentiation, cell adhesion, cell clustering, tissue induction and organogenesis have been observed, but the molecular mechanism of high temperature teratogenesis has not yet been clarified. NTDs induced by high temperature is an extremely complex process, in which some proteins are synthesized, especially with embryonic differentiation.
【学位授予单位】：山东大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R321.6

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