【作者】 吴传新；

【导师】 龚建平；

【作者基本信息】 重庆医科大学 ， 外科学， 2006， 博士

【摘要】 目的:脓毒症是由细菌感染引起的一种致死性、全身性炎症反应,是临床危重患者主要的死亡原因之一。脓毒症发生发展的根本原因在于机体过度释放细胞因子和炎性介质,导致炎症反应失控和免疫功能紊乱。因此,细胞因子和炎性介质在脓毒症的发生发展中起十分重要的作用。高迁移率族蛋白B1(high mobility group protein B1,HMGB1)是近年研究发现的脓毒症“晚期”炎性介质,是脓毒症发生发展中起关键性作用的细胞因子,其在脓毒症中的作用得到越来越多的关注和重视,但脓毒症时HMGB1释放的具体分子机制尚未完全阐明。本研究拟首先采用内毒素(脂多糖,lipoplysaccharide,LPS)刺激巨噬细胞,观察LPS刺激后巨噬细胞中HMGB1、肿瘤坏死因子α(Tumor necrosis factor alpha ,TNF-α)和白细胞介素6 (Interleukin-6,IL-6)释放和表达的水平,并测定LPS刺激后巨噬细胞核转录因子-κB (Nuclear facror kappa B , NF-κB )、P38丝裂原活化蛋白激酶( P38 Mitogen-activated protein kinase,p38MAPK)和CREB结合蛋白(CREB binding protein,CBP)的活性变化,以期阐明LPS刺激巨噬细胞HMGB1释放的规律及其分子机制;其次,分别采用LPS、LPS+丙酮酸乙酯刺激巨噬细胞,检测巨噬细胞HMGB1、TNF-α、IL-6释放和表达的水平,并测定巨噬细胞NF-κB、p38MAPK、CBP的活性变化,比较LPS和LPS+丙酮酸乙酯刺激后巨噬细胞HMGB1释放和表达水平的变化以及更多还原

【Abstract】 objective:Sepsis is a lethal systemic inflammatory reaction caused by bacterial infection. It is one main causes of death in clinical severe patients. The basic reason of sepsis happened and developed is the excessive delivery of cytokines and inflammatory mediators by organism, which leads to the inflammatory reaction loss of control and immune function disorder. Therefore, the cytokines and inflammatory mediators play an important role in the development of sepsis. High mobility group protein box1 (HMGB1) is a kind of advanced stage inflammatory mediators discovered recently. It is the critical inflammatory mediators in generation and development of sepsis. And more and more people pay close attention to it’s role in sepsis. But the molecule mechanisms of HMGB1 release in sepsis are still unknown. Firstly, we used endotoxin (lipopolysaccharide,LPS) to stimulate macrophages and observed the releasing and expressing level of HMGB1, tumor necrosis factor alpha (TNF-α) and Interleukin-6 (IL-6).Then we determined the activity changes of Nuclear factor kappa B (NF-κB)﹑P38 mitogen activated protein kinase (p38MAPK) and CREB binding protein (CBP), in order to elucidate the release rule and molecule mechanisms of HMGB1 after stimulated by LPS. Secondly, we detected the releasing and expressing level of HMGB1, TNF-αand IL-6 in macrophages stimulated by LPS﹑LPS+ethyl pyruvate(EP) respectively更多还原