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靶向stat3基因干擾對小鼠神經干細胞增殖分化影響的實驗研究

發(fā)布時間:2018-04-26 23:13

  本文選題:神經上皮 + 神經干細胞; 參考:《第三軍醫(yī)大學》2006年碩士論文


【摘要】:神經系統(tǒng)是機體最重要和最復雜的系統(tǒng),起源于神經管(neural tube)和神經嵴,神經管形成中樞神經系統(tǒng)(central nervous system,CNS)(腦和脊髓),神經嵴形成周圍神經系統(tǒng)的神經節(jié)等。CNS正常發(fā)生的關鍵是神經板內外相關組織細胞行為的準確進行和協(xié)同,神經管的形成是該過程結束的標志。神經管發(fā)生是一個重要的涉及到建立中樞神經系統(tǒng)原基的胚胎學事件,是指從神經板出現到神經管關閉的發(fā)育過程。神經管管壁最初是由一層較厚的假復層上皮組成,稱為神經上皮(neuroepithenium)。神經上皮不斷增殖的同時細胞也逐漸開始進行遷移和分化,逐漸形成三層結構的管壁,由內向外依次為室管膜層,套層和邊緣層。在此過程中,神經上皮細胞處于活躍的細胞增殖周期中,為具有多種分化潛能的神經干細胞,伴隨著分化演變。神經上皮中神經干細胞的增殖遷移以及分化是神經系統(tǒng)發(fā)育的關鍵環(huán)節(jié)。研究發(fā)現神經管形成時期極易受多種內外因素的干擾而致畸,神經管缺陷(neural tube defect,NTD)就是其中發(fā)病率最高的一種,表現為各種腦和脊髓的發(fā)育畸形。多年來的研究提示NTD的發(fā)生與神經上皮的異常發(fā)育密切相關。從基因水平而言,,神經上皮的發(fā)育過程是一系列基因按照高度特異的時空模式表達并相互作用的結果,但迄今對此復雜過程的基因表達與調控的了解還很少。 信號轉導與轉錄激活因子3(signal transducer and activator of transcription 3,STAT3)是STAT家族的成員之一,作為重要的信號轉導因子,參與多種基因的表達和調控,并與其他轉錄因子一起形成復雜的調控網絡,已證實參與到胚胎的神經系統(tǒng)、眼發(fā)育等過程中。神經管閉合后,神經管上皮細胞進一步增生、分化和遷移,其前段呈現三個膨大,依次稱為前腦泡、中腦泡和菱腦泡。神經管上皮細胞的增生、分化和遷移對于神經系統(tǒng)正常結構和功能的建立十分重要。紀華等通過原位雜交等技術檢測STAT3mRNA在E9.5-E11.5的小鼠胚胎中的表達情況,結果依次顯示為起始的前腦泡劇增、轉移至中腦泡、最后僅存于菱腦泡中的狹窄區(qū)域。提示STAT3可能參與了神經管頭段的區(qū)域化,即前腦、中腦、菱腦三個腦泡的形成。 已有研究發(fā)現,STAT3蛋白在植入后胚胎中即開始有所表達,尤其是在E10.5至
[Abstract]:The nervous system is the most important and complex system of the body, originating from neural tubes and neural crest. The key to the normal occurrence of CNS in the central nervous system, such as the brain and spinal cord, the formation of peripheral nervous system ganglion, etc., is the accurate and synergistic behavior of the related histocytes inside and outside the nerve plate. The formation of a neural tube marks the end of the process. Neurotubulogenesis is an important embryological event involved in the establishment of the primordium of the central nervous system (CNS) and refers to the developmental process from the appearance of the nerve plate to the closure of the neural tube. The neural tube wall was originally composed of a thicker pseudostratified epithelium called neuroepithelial epithelium. At the same time the neural epithelium proliferated and the cells began to migrate and differentiate gradually forming a three-layer structure of the wall from the inside to the outside of the ependymal layer sleeve layer and marginal layer. In this process, neuroepithelial cells are active in the cell proliferation cycle, neural stem cells with multiple differentiation potential, with the evolution of differentiation. The proliferation, migration and differentiation of neural stem cells in neural epithelium are the key to the development of nervous system. It has been found that neural tube formation is easily affected by many internal and external factors, and neural tube defectNTD is one of the most common deformity of brain and spinal cord. Years of studies have shown that the occurrence of NTD is closely related to abnormal development of neuroepithelium. At the gene level, the developmental process of neuroepithelium is the result of a series of genes expressed and interacted according to a highly specific spatiotemporal pattern, but so far little has been known about the gene expression and regulation of this complex process. As an important signal transduction factor, signal transduction and transcriptional activator (3(signal transducer and activator of transcription _ 3 / STAT _ 3) is a member of the STAT family. As an important signal transduction factor, it participates in the expression and regulation of many genes and forms a complex regulatory network with other transcription factors. It has been proved to be involved in the embryonic nervous system, eye development, etc. After the closure of the neural tube, the epithelial cells of the neural tube were further proliferated, differentiated and migrated. The anterior segment of the neural tube showed three enlargement, which were called forebrain vesicles, mesencephalic vesicles and rhomboid vesicles in turn. The proliferation, differentiation and migration of neural tube epithelial cells are very important for the establishment of normal structure and function of nervous system. Ji Hua et al detected the expression of STAT3mRNA in mouse embryos of E9.5-E11.5 by in situ hybridization. The results showed that the initial forebrain vesicles increased sharply and metastasized to the mesencephalic vesicles, and finally only in the narrow areas of the rhomboid vesicles. The results suggest that STAT3 may be involved in the formation of three brain vesicles in the forebrain, midbrain and rhomboid. It has been found that STAT3 protein begins to express in post-implantation embryos, especially in E10.5 to E10.5.
【學位授予單位】:第三軍醫(yī)大學
【學位級別】:碩士
【學位授予年份】:2006
【分類號】:R346

【參考文獻】

相關期刊論文 前1條

1 紀華,李澤桂,馬路,丁震宇,蔡文琴,傅新元,常智杰,劉力;STAT3在小鼠胚胎神經系統(tǒng)發(fā)育中的表達[J];第三軍醫(yī)大學學報;2005年07期



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