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高溫致畸金黃地鼠胚胎神經(jīng)管cDNA文庫(kù)的構(gòu)建及致畸相關(guān)基因的篩查

發(fā)布時(shí)間:2019-06-28 17:33
【摘要】:在脊椎動(dòng)物胚胎發(fā)育過(guò)程中,神經(jīng)胚是一個(gè)重要的發(fā)育時(shí)期。這個(gè)階段胚胎外胚層增厚形成上皮性神經(jīng)板,神經(jīng)板兩側(cè)隆起形成神經(jīng)褶,隨后神經(jīng)褶兩側(cè)向背中線靠攏并愈合成神經(jīng)管。神經(jīng)管的發(fā)生和分化是腦和脊髓正常發(fā)育的前提,這一發(fā)育過(guò)程發(fā)生異常就會(huì)導(dǎo)致神經(jīng)管畸形(neural tube defects,NTDs)。隨著現(xiàn)代工業(yè)的發(fā)展和環(huán)境污染的日趨嚴(yán)重,人類先天畸形的發(fā)生率也逐年上升。1986年調(diào)查結(jié)果顯示,我國(guó)新生兒先天畸形的發(fā)生率高達(dá)1.3%,因此,對(duì)先天畸形的研究越來(lái)越受到人們的重視。在各類先天畸形中,神經(jīng)管畸形是發(fā)生率最高、危害也最為嚴(yán)重的一類先天畸形,由胚胎發(fā)育早期神經(jīng)管閉合不全或延遲閉合所致,主要涉及中樞神經(jīng)系統(tǒng),包括無(wú)腦、露腦、脊柱裂等。神經(jīng)管畸形也是導(dǎo)致死胎、流產(chǎn)和早產(chǎn)的主要原因之一,其致殘率很高,給家庭和社會(huì)帶來(lái)嚴(yán)重的心理和經(jīng)濟(jì)負(fù)擔(dān)。NTDs的病因非常復(fù)雜,既有遺傳因素,也有環(huán)境因素,更包含著遺傳因素與環(huán)境因素之間的交互作用。 流行病學(xué)調(diào)查及動(dòng)物實(shí)驗(yàn)顯示,高溫是最常見(jiàn)且難以預(yù)防的一種物理致畸因子,,可引起多種動(dòng)物以及人類的先天畸形,其中以NTDs的出現(xiàn)率最高。近年來(lái),各國(guó)學(xué)者在高溫致畸方面作了大量的動(dòng)物實(shí)驗(yàn)和細(xì)胞培養(yǎng)研究,觀察了高溫對(duì)細(xì)胞增殖、細(xì)胞凋亡、細(xì)胞分化、細(xì)胞粘著、細(xì)胞類聚、組織誘導(dǎo)和器官發(fā)生等方面的影響,取得了不少成果,但至今仍未闡明高溫致畸的分子機(jī)理。高溫致NTDs是一個(gè)極其復(fù)雜的過(guò)程,在這個(gè)過(guò)程中,有些蛋白質(zhì)的合成,尤其是與胚胎分化
[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.
【學(xué)位授予單位】:山東大學(xué)
【學(xué)位級(jí)別】:博士
【學(xué)位授予年份】:2006
【分類號(hào)】:R321.6

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