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  本文關鍵詞： C56 補體攻膜復合物 中樞神經系統(tǒng) 小膠質細胞 Aβ NO_2~- TNF-α 共刺激分子 CD40　出處：《第三軍醫(yī)大學》2006年碩士論文　論文類型：學位論文

【摘要】： 背景: 中樞神經系統(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,成為機體組織中的免疫赦免區(qū),但事實上CNS內環(huán)境的穩(wěn)定仍需依靠天然免疫系統(tǒng)的長期監(jiān)視和保護;其中,CNS內免疫活性最強的小膠質細胞和腦組織自身局部產生的補體系統(tǒng),作為天然免疫的重要成分,是CNS內重要的防御力量,若它們的的代謝及功能出現(xiàn)紊亂則會導致內環(huán)境失衡,炎癥爆發(fā),大量炎細胞激活、炎癥因子釋放等,對自身正常組織產生“旁觀殺傷效應”[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)為進行性記憶和后天獲得性知識不可逆性損失的漸進性神經退行性疾病,其發(fā)病的始動因素是細胞外大量的淀粉樣蛋白Aβ(β-amyloid)的沉積,從而促發(fā)了小膠質細胞和補體系統(tǒng)的活化失控及功能異常,炎癥因子大量釋放,最終導致神經纖維纏結、膽堿能神經元喪失,自身神經組織受到損害。AD是一種自身毒性改變而非自身免疫性損傷,炎癥反應在其中起到了關鍵的作用[4]。 目前認為,小膠質細胞是CNS內最主要的免疫活性細胞,它既可表現(xiàn)為骨髓源單核細胞系統(tǒng)的吞噬活性,又可表現(xiàn)出活化后的致炎效應。研究證實,AD病變早期,活化小膠質細胞可對Aβ產生吞噬作用,但隨著炎癥的發(fā)展,大量沉積的Aβ不斷刺激小膠質細胞活化,使其功能紊亂代謝失衡,對Aβ的吞噬減少,同時分泌大量炎性介質和氧自由基,上調表達多種免疫分子,對神經組織造成損傷并促進炎癥的進一步加深[5]。 補體系統(tǒng)是CNS內重要的天然免疫防御系統(tǒng),當病原微生物或炎性介質存在時可被激活最終通過末端成分組裝成C5b-9_((n))膜攻擊復合物(membrane attack complex, MAC)。C5b-9_((n))是CNS炎癥過程中一種多效免疫因子,在補體大量活化后,可插入細胞膜導致細胞溶解死亡,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】：R392

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3 劉p，

本文編號：1497416