IRAK-M在内毒素耐受形成机制中作用的实验研究

发布时间：2018-05-29 23:16

本文选题：RNA + 干扰　；参考：《重庆医科大学》2005年博士论文

【摘要】：脓毒症(sepsis)至今仍是临床治疗中的难点,其导致的死亡率高达 30-40%,而在所有脓毒症病例中,由革兰氏阴性(G-)细菌感染引起者约占 60%。内毒素又名脂多糖(lipopolysaccharide, LPS),是 G-细菌细胞壁上的主要成分,也是 G-细菌最为重要的致病物质,它能激活单核-巨噬细胞系统(mononuclear phagocytic system, MPS),引起TNF-α 等大量前炎症介质释放,导致全身炎症反应综合征(systemic inflammatory response syndrome, SIRS)及器官损害。然而,机体在遭受LPS刺激的同时也能产生相应的保护机制——即内毒素耐受(endotoxin tolerance)状态。所谓内毒素耐受是指:机体或单核-巨噬细胞经LPS预处理后,对LPS的再次刺激呈低反应性。目前认为,内毒素耐受是生物在长期进化过程中形成的一种保守的负反馈调节机制,是一种适应性应答,能避免了机体对LPS刺激的持续过度反应,是机体防御机制的重要组成部分。最近的研究表明,白介素1受体相关激酶-M(IRAK-M)对LPS信号通路起负性调节作用,从而有可能参与内毒素耐受的形成机制。本研究通过建立内毒素耐受的小鼠及Kupffer细胞模型,观察在内毒毒耐受状态下机体及细胞中IRAK-M表达的变化,初步确定IRAK-M与内毒素耐受的关系;进而采用RNA干扰技术在体外沉寂IRAK-M的基因表
[Abstract]:Sepsis (sepsis) is still a difficult point in clinical treatment, and the mortality rate is as high as 30-40%. In all cases of sepsis, about 60 cases are caused by Gram-negative G-negative bacterial infection. Lipopolysaccharide, also known as lipopolysaccharide, is the main component in the cell wall of G- bacteria and the most important pathogenic substance of G- bacteria. It can activate mononuclear phagocytic system (MPSN) of mononuclear macrophage system and induce the release of a large number of proinflammatory mediators, such as TNF- 伪. Lead to systemic inflammatory response syndrome, systemic inflammatory response syndrome, SIRS) and organ damage. However, LPS stimulates the body to produce the protective mechanism of endotoxin tolerance. Endotoxin tolerance means that the body or mononuclear macrophages pretreated with LPS are hyporeactive to the restimulation of LPS. It is believed that endotoxin tolerance is a kind of conservative negative feedback regulation mechanism formed in the long evolution of organism, and it is an adaptive response, which can avoid the persistent overreaction of organism to LPS stimulation. It is an important part of the body defense mechanism. Recent studies have shown that interleukin-1 receptor-associated kinases (IL-1 receptor-associated kinases) -MRAK-M1 play a negative role in the LPS signaling pathway, which may be involved in the formation of endotoxin tolerance. In order to determine the relationship between endotoxin tolerance and endotoxin tolerance, the changes of IRAK-M expression in body and cells were observed by establishing endotoxin tolerant mice and Kupffer cell models. Then RNA interference technique was used to silence the gene surface of IRAK-M in vitro.
【学位授予单位】：重庆医科大学
【学位级别】：博士
【学位授予年份】：2005
【分类号】：R363

【共引文献】