亚溶破补体攻膜复合物对小胶质细胞刺激效应的研究

发布时间：2018-02-09 07:35

本文关键词： C56 补体攻膜复合物中枢神经系统小胶质细胞 Aβ NO_2~- TNF-α 共刺激分子 CD40　出处：《第三军医大学》2006年硕士论文　论文类型：学位论文

【摘要】： 背景: 中枢神经系统(central nervous system,CNS)由于免疫抑制微环境和血脑屏障(blood-brain barrier,BBB)[1]这两道天然屏障的的存在,成为机体组织中的免疫赦免区,但事实上CNS内环境的稳定仍需依靠天然免疫系统的长期监视和保护;其中,CNS内免疫活性最强的小胶质细胞和脑组织自身局部产生的补体系统,作为天然免疫的重要成分,是CNS内重要的防御力量,若它们的的代谢及功能出现紊乱则会导致内环境失衡,炎症爆发,大量炎细胞激活、炎症因子释放等,对自身正常组织产生“旁观杀伤效应”[2, 3]。大量研究显示:阿尔茨海默病(Alzheimer’s disease, AD)是一种临床表现为进行性记忆和后天获得性知识不可逆性损失的渐进性神经退行性疾病,其发病的始动因素是细胞外大量的淀粉样蛋白Aβ(β-amyloid)的沉积,从而促发了小胶质细胞和补体系统的活化失控及功能异常,炎症因子大量释放,最终导致神经纤维缠结、胆碱能神经元丧失,自身神经组织受到损害。AD是一种自身毒性改变而非自身免疫性损伤,炎症反应在其中起到了关键的作用[4]。目前认为,小胶质细胞是CNS内最主要的免疫活性细胞,它既可表现为骨髓源单核细胞系统的吞噬活性,又可表现出活化后的致炎效应。研究证实,AD病变早期,活化小胶质细胞可对Aβ产生吞噬作用,但随着炎症的发展,大量沉积的Aβ不断刺激小胶质细胞活化,使其功能紊乱代谢失衡,对Aβ的吞噬减少,同时分泌大量炎性介质和氧自由基,上调表达多种免疫分子,对神经组织造成损伤并促进炎症的进一步加深[5]。补体系统是CNS内重要的天然免疫防御系统,当病原微生物或炎性介质存在时可被激活最终通过末端成分组装成C5b-9_((n))膜攻击复合物(membrane attack complex, MAC)。C5b-9_((n))是CNS炎症过程中一种多效免疫因子,在补体大量活化后,可插入细胞膜导致细胞溶解死亡,而近年来新的研究发现,非致死剂量的MAC可沉积于中
[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
【学位授予单位】：第三军医大学
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R392

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