【摘要】：神經(jīng)系統(tǒng)是機(jī)體最重要和最復(fù)雜的系統(tǒng),而其中神經(jīng)管的發(fā)生是一個(gè)重要的涉及到建立中樞神經(jīng)系統(tǒng)(central nervous system, CNS)原基的胚胎學(xué)事件,是指從神經(jīng)板出現(xiàn)到神經(jīng)管關(guān)閉的發(fā)育過(guò)程。在這個(gè)過(guò)程中,神經(jīng)板必須準(zhǔn)時(shí)準(zhǔn)確地關(guān)閉形成神經(jīng)管,神經(jīng)系統(tǒng)才能得以正常發(fā)育;否則將出現(xiàn)神經(jīng)管缺陷(neural tube defect, NTD),表現(xiàn)為各種腦和脊髓的發(fā)育畸形,如脊柱裂、露腦畸形等。露腦患兒均不能存活,脊柱裂患兒視情況而定,特別影響社會(huì)勞動(dòng)力的是一些隱性脊柱裂患者,他們均給家庭和社會(huì)帶來(lái)了嚴(yán)重的負(fù)擔(dān)。為此,近一個(gè)多世紀(jì)以來(lái),胚胎學(xué)家和發(fā)育神經(jīng)生物學(xué)家堅(jiān)持不懈地應(yīng)用了許多不同的動(dòng)物模型和不同的實(shí)驗(yàn)技術(shù),試圖探討從神經(jīng)板出現(xiàn)到神經(jīng)管閉合這一涉及多因素調(diào)控的過(guò)程及機(jī)理,以避免和預(yù)防NTD 的發(fā)生,所以正常神經(jīng)管形成的分子機(jī)制和NTD 的發(fā)病機(jī)理已成為當(dāng)今神經(jīng)科學(xué)研究的熱點(diǎn)和前沿。 神經(jīng)管閉合后,神經(jīng)管上皮細(xì)胞的進(jìn)一步增生、分化和遷移對(duì)于神經(jīng)系統(tǒng)正常形態(tài)和功能的建立十分重要。它的前端呈現(xiàn)三個(gè)膨大,依次稱為前腦泡、中腦泡和菱腦泡,前腦泡發(fā)育為端腦和間腦,中腦泡發(fā)育為中腦,菱腦泡的前部發(fā)育為后腦,以后演變?yōu)槟X橋和小腦,菱腦泡的后部發(fā)育為延髓,神經(jīng)管尾端形成未來(lái)的脊髓。神經(jīng)管發(fā)生和神經(jīng)管關(guān)閉后的神經(jīng)上皮細(xì)胞繼續(xù)發(fā)育、分化和遷移,直至最終形成結(jié)構(gòu)正常和功能完善的CNS,從基因水平而言,上述過(guò)程是一系列基因按照高度特異的時(shí)空模式表達(dá)并相互作用的結(jié)果。 已知氧是保證各種生命活動(dòng)最基本和最重要的因素,近年的研究證實(shí)人類胚胎、大鼠及小鼠胚胎發(fā)育中均存在低氧區(qū),那么作為體內(nèi)對(duì)低氧的重要調(diào)節(jié)因子——低氧誘導(dǎo)因子-1(hypoxia-inducible factor-1, HIF-1)是否參與其中呢?已有研究發(fā)現(xiàn)HIF-1α-/-小鼠顯示有神經(jīng)發(fā)育缺陷,包含神經(jīng)管未閉和腦血管發(fā)育異常。但HIF-1α表達(dá)缺失是怎樣影響神經(jīng)管關(guān)閉的呢?確切的作用和分子機(jī)制又是什么呢?其在涉及NTD 發(fā)生的眾多基因中是否處于調(diào)節(jié)者的地位呢?近年研究發(fā)現(xiàn),有許多基因參與中樞神經(jīng)系統(tǒng)發(fā)育的調(diào)控,外環(huán)境也是通過(guò)這些基因發(fā)揮作用的。作為參與體內(nèi)對(duì)低氧調(diào)節(jié)的重要轉(zhuǎn)錄因子HIF-1,是否可能通過(guò)啟動(dòng)不同靶基因表達(dá)來(lái)參與神經(jīng)管上皮細(xì)胞的增生、分化和遷移
[Abstract]:The nervous system is the most important and complex system in the body, and the occurrence of neural tubes is an important embryological event that involves the establishment of the (central nervous system, CNS) primordium of the central nervous system. It refers to the developmental process from the appearance of the nerve plate to the closure of the neural tube. In this process, the nerve plate must be closed on time and accurately to form the neural tube, so that the nervous system can develop normally. Otherwise, neural tube defect (neural tube defect, NTD),) will appear as various developmental malformation of brain and spinal cord, such as spina bifida, brain deformity and so on. None of the children with exposed brain can survive, and the children with spina bifida depend on the situation. It is some recessive spina bifida patients who especially affect the social labor force, and they all bring serious burden to the family and society. For more than a century, embryologists and developmental neurobiologists have persistently applied many different animal models and different experimental techniques. In order to avoid and prevent the occurrence of NTD, we tried to explore the process and mechanism of multi-factor regulation from the appearance of nerve plate to the closure of neural tube. Therefore, the molecular mechanism of normal neural tube formation and the pathogenesis of NTD have become the focus and frontier of neuroscience. After neural tube closure, the proliferation, differentiation and migration of neural tube epithelial cells are very important for the establishment of normal morphology and function of nervous system. Its front end presents three dilated brain bubbles, in turn called forebrain vesicles, midbrain vesicles and rhomboid vesicles. Forebrain vesicles develop into telencephalons and diencephalons, midbrain bubbles develop into mesencephalons, and the forepart of rhomboid vesicles develops into posterior brains, and then develops into pons and cerebellum. The posterior part of the rhombic vesicle develops into the medulla oblongata and the caudal end of the canal forms the future spinal cord. Neuroepithelial cells from neurogenesis and closure continue to develop, differentiate, and migrate until they eventually form a well-structured and well-functioning CNS, at the genetic level. These processes are the result of a series of genes expressed in a highly specific spatio-temporal pattern and interacting with each other. Oxygen is known to be the most basic and important factor to ensure all kinds of life activities. Recent studies have confirmed that hypoxia exists in the development of human embryos, rat embryos and mouse embryos. So is hypoxia-inducible factor-1 (hypoxia-inducible factor-1, HIF-1), an important regulator of hypoxia in vivo, involved in it? It has been found that HIF-1 偽-/-mice have neurodevelopmental defects, including neural canal patent and cerebral vascular dysplasia. But how does the lack of expression of HIF-1 偽 affect the closure of neural tubes? What are the exact roles and molecular mechanisms? Is it a regulator among the many genes involved in the occurrence of NTD? In recent years, it has been found that many genes are involved in the regulation of central nervous system development, and the external environment is also involved in the regulation of the development of the central nervous system. Whether HIF-1, an important transcription factor involved in the regulation of hypoxia in vivo, may participate in the proliferation, differentiation and migration of neural tube epithelial cells by initiating the expression of different target genes.
【學(xué)位授予單位】：第三軍醫(yī)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2005
【分類號(hào)】：R321

【相似文獻(xiàn)】

相關(guān)期刊論文 前10條

1 紀(jì)華,李澤桂,丁震宇,馬路,李紅麗,蔡文琴,常智杰,劉力,傅新元;FGF8在神經(jīng)胚形成和NTD中的表達(dá)變化及其與STAT3的關(guān)系研究[J];第三軍醫(yī)大學(xué)學(xué)報(bào);2005年14期

2 Ｇ．ＷａｙｎｅＢｒｏｄｌａｎｄ,陳紅;計(jì)算機(jī)模擬在胚胎形態(tài)發(fā)育機(jī)理研究中的最新進(jìn)展及前景[J];力學(xué)進(jìn)展;1997年04期

3 紀(jì)華,李澤桂,馬路,丁震宇,蔡文琴,傅新元,常智杰,劉力;STAT3在小鼠胚胎神經(jīng)系統(tǒng)發(fā)育中的表達(dá)[J];第三軍醫(yī)大學(xué)學(xué)報(bào);2005年07期

4 林浴霜;陳冬艷;范秋聲;張紅衛(wèi);;關(guān)于青島文昌魚SoxB2和SoxC基因的研究:進(jìn)化保守性分析[J];中國(guó)科學(xué)(C輯:生命科學(xué));2009年05期

5 李澤桂,蔡文琴,陳活彝;神經(jīng)管發(fā)生中的形態(tài)學(xué)事件和分子機(jī)制[J];第三軍醫(yī)大學(xué)學(xué)報(bào);1999年08期

6 曾彌白,王新明;有尾兩棲類細(xì)胞連接和神經(jīng)管形成[J];實(shí)驗(yàn)生物學(xué)報(bào);1984年02期

7 張士璀,袁金鐸,李紅巖;文昌魚──研究脊椎動(dòng)物起源和進(jìn)化的模式動(dòng)物[J];生命科學(xué);2001年05期

8 孫榆,李澤桂,蔡文琴;轉(zhuǎn)染重組bcl-2基因緩解RA介導(dǎo)NTCD的電鏡觀察[J];四川解剖學(xué)雜志;2001年02期

9 李澤桂,蔡文琴;小鼠神經(jīng)管發(fā)生中PCD與原癌基因bcl-2表達(dá)的相關(guān)性[J];四川解剖學(xué)雜志;2001年01期

10 孫秀寧,管英俊,岳炳德,張皓云;巢蛋白在中樞神經(jīng)系統(tǒng)發(fā)育及損傷后再生過(guò)程中的作用[J];濰坊醫(yī)學(xué)院學(xué)報(bào);2005年01期

相關(guān)博士學(xué)位論文 前1條

1 高永輝;PARD3基因單核苷酸多態(tài)性和拷貝數(shù)變異與神經(jīng)管畸形發(fā)生的相關(guān)性研究[D];北京協(xié)和醫(yī)學(xué)院;2012年

相關(guān)碩士學(xué)位論文 前1條

1 丁震宇;HIF-1α在小鼠胚胎神經(jīng)系統(tǒng)發(fā)育中的表達(dá)及其RNAi的相關(guān)實(shí)驗(yàn)研究[D];第三軍醫(yī)大學(xué);2005年

，

本文編號(hào)：2430432