本文關(guān)鍵詞： C56 補(bǔ)體攻膜復(fù)合物 中樞神經(jīng)系統(tǒng) 小膠質(zhì)細(xì)胞 Aβ NO_2~- TNF-α 共刺激分子 CD40　出處：《第三軍醫(yī)大學(xué)》2006年碩士論文　論文類型：學(xué)位論文

【摘要】： 背景: 中樞神經(jīng)系統(tǒng)(central nervous system,CNS)由于免疫抑制微環(huán)境和血腦屏障(blood-brain barrier,BBB)[1]這兩道天然屏障的的存在,成為機(jī)體組織中的免疫赦免區(qū),但事實(shí)上CNS內(nèi)環(huán)境的穩(wěn)定仍需依靠天然免疫系統(tǒng)的長(zhǎng)期監(jiān)視和保護(hù);其中,CNS內(nèi)免疫活性最強(qiáng)的小膠質(zhì)細(xì)胞和腦組織自身局部產(chǎn)生的補(bǔ)體系統(tǒng),作為天然免疫的重要成分,是CNS內(nèi)重要的防御力量,若它們的的代謝及功能出現(xiàn)紊亂則會(huì)導(dǎo)致內(nèi)環(huán)境失衡,炎癥爆發(fā),大量炎細(xì)胞激活、炎癥因子釋放等,對(duì)自身正常組織產(chǎn)生“旁觀殺傷效應(yīng)”[2, 3]。 大量研究顯示:阿爾茨海默病(Alzheimer’s disease, AD)是一種臨床表現(xiàn)為進(jìn)行性記憶和后天獲得性知識(shí)不可逆性損失的漸進(jìn)性神經(jīng)退行性疾病,其發(fā)病的始動(dòng)因素是細(xì)胞外大量的淀粉樣蛋白Aβ(β-amyloid)的沉積,從而促發(fā)了小膠質(zhì)細(xì)胞和補(bǔ)體系統(tǒng)的活化失控及功能異常,炎癥因子大量釋放,最終導(dǎo)致神經(jīng)纖維纏結(jié)、膽堿能神經(jīng)元喪失,自身神經(jīng)組織受到損害。AD是一種自身毒性改變而非自身免疫性損傷,炎癥反應(yīng)在其中起到了關(guān)鍵的作用[4]。 目前認(rèn)為,小膠質(zhì)細(xì)胞是CNS內(nèi)最主要的免疫活性細(xì)胞,它既可表現(xiàn)為骨髓源單核細(xì)胞系統(tǒng)的吞噬活性,又可表現(xiàn)出活化后的致炎效應(yīng)。研究證實(shí),AD病變?cè)缙?活化小膠質(zhì)細(xì)胞可對(duì)Aβ產(chǎn)生吞噬作用,但隨著炎癥的發(fā)展,大量沉積的Aβ不斷刺激小膠質(zhì)細(xì)胞活化,使其功能紊亂代謝失衡,對(duì)Aβ的吞噬減少,同時(shí)分泌大量炎性介質(zhì)和氧自由基,上調(diào)表達(dá)多種免疫分子,對(duì)神經(jīng)組織造成損傷并促進(jìn)炎癥的進(jìn)一步加深[5]。 補(bǔ)體系統(tǒng)是CNS內(nèi)重要的天然免疫防御系統(tǒng),當(dāng)病原微生物或炎性介質(zhì)存在時(shí)可被激活最終通過末端成分組裝成C5b-9_((n))膜攻擊復(fù)合物(membrane attack complex, MAC)。C5b-9_((n))是CNS炎癥過程中一種多效免疫因子,在補(bǔ)體大量活化后,可插入細(xì)胞膜導(dǎo)致細(xì)胞溶解死亡,而近年來新的研究發(fā)現(xiàn),非致死劑量的MAC可沉積于中
[Abstract]:Background:. Central nervous system (CNS) has become the immune pardoned area in the organism because of the existence of immune suppressive microenvironment and blood-brain barrier barrier [1]. However, in fact, the stability of the internal environment of CNS still depends on the long-term monitoring and protection of the innate immune system, in which microglia, the most active microglia, and the complement system produced locally in brain tissue are important components of innate immunity. It is an important defense force in CNS. If their metabolism and function are disordered, they will lead to the imbalance of internal environment, the outbreak of inflammation, the activation of a large number of inflammatory cells, the release of inflammatory factors, and so on, resulting in "bystander killing effect" on their normal tissues [2,3]. A large number of studies have shown that Alzheimer's disease (ADD) is a progressive neurodegenerative disease characterized by irreversible loss of progressive memory and acquired knowledge. The initiation factor of its pathogenesis is the deposition of a large amount of extracellular amyloid A 尾 (尾 -amyloid), which promotes the activation of microglia and complement system out of control and abnormal function, and the release of a large number of inflammatory factors, which eventually leads to the tangles of nerve fibers. Loss of cholinergic neurons and damage to autonerve tissue. AD is an autotoxic change rather than an autoimmune injury in which inflammatory response plays a key role [4]. At present, microglia are considered to be the most important immunoreactive cells in CNS, which can be expressed as phagocytic activity of monocyte system derived from bone marrow and inflammatory effect after activation. Activation of microglia could induce phagocytosis of A 尾, but with the development of inflammation, a large amount of deposited A 尾 stimulated the activation of microglia and caused the dysfunction of metabolism, and decreased the phagocytosis of A 尾. At the same time, a large number of inflammatory mediators and oxygen free radicals were secreted, and a variety of immune molecules were up-regulated and expressed, which caused damage to nerve tissue and promoted the further deepening of inflammation [5]. Complement system is an important innate immune defense system in CNS. When pathogenic microorganisms or inflammatory mediators are present, they can be activated and eventually assembled by terminal components to form C5b-9) membrane attack complex (MACU. C5b-9) is a multipotent immune factor in the process of CNS inflammation. After a large number of complement activation, inserted into the cell membrane, resulting in cell lysis and death, and in recent years, new research found that the non-lethal dose of MAC can be deposited in the
【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】：2006
【分類號(hào)】：R392

【共引文獻(xiàn)】

相關(guān)期刊論文 前7條

1 吳佩澤;華樹成;楊雪梅;;補(bǔ)體攻膜復(fù)合物C5b-9處理后的樹突狀細(xì)胞對(duì)同種異體淋巴細(xì)胞的作用[J];吉林大學(xué)學(xué)報(bào)(醫(yī)學(xué)版);2008年01期

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3 楊玉璽;黃頌敏;顏曉勇;吳蔚樺;;糖尿病腎病模型中NF-κB與甘露聚糖結(jié)合凝集素途徑補(bǔ)體激活的關(guān)系[J];四川大學(xué)學(xué)報(bào)(醫(yī)學(xué)版);2011年04期

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2 趙志伶;CVF和涼膈散對(duì)創(chuàng)傷失血性休克大鼠肝臟損害機(jī)制的研究[D];天津醫(yī)科大學(xué);2011年

3 高玲娟;Sublytic C5b-9誘導(dǎo)GMCs增殖和ECM分泌分子機(jī)制及其信號(hào)通路[D];南京醫(yī)科大學(xué);2007年

4 侯寧寧;鏈脲佐菌素誘導(dǎo)的糖尿病大鼠外周神經(jīng)病變免疫損傷和環(huán)孢素A的抑制作用[D];天津醫(yī)科大學(xué);2007年

5 王慧;Sublytic C5b-9誘導(dǎo)Thy-1腎炎GMCs凋亡的機(jī)制研究[D];南京醫(yī)科大學(xué);2008年

6 李文博;補(bǔ)體C5b-9復(fù)合物對(duì)人RPE細(xì)胞膜通透性及VEGF、TGF-β2表達(dá)的影響[D];天津醫(yī)科大學(xué);2008年

7 李莉;草魚補(bǔ)體C9和穿孔素基因的克隆與表達(dá)研究[D];華中農(nóng)業(yè)大學(xué);2008年

8 安貴鵬;補(bǔ)體抗動(dòng)脈粥樣硬化和調(diào)節(jié)Toll樣受體致炎作用的實(shí)驗(yàn)研究[D];山東大學(xué);2009年

相關(guān)碩士學(xué)位論文 前6條

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2 姜孝明;ATF3在sublyticC5b-9復(fù)合物誘導(dǎo)GMCs凋亡中的作用[D];南京醫(yī)科大學(xué);2009年

3 劉p，

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