中文摘要：

内毒素耐受（endotoxin tolerance）早在50多年前就已经引起人们的关注，但其具体的分子机制至今尚不清楚。Toll样受体4（Toll-1ike receptor-4，TLR4）作为脂多糖（LPS）的主要受体，参与LPS信号的跨膜转导，与LPS耐受密切相关。在内毒素耐受过程中，TLR4转导通路中的信号蛋白及下游转录因子在数量、结构和功能上发生改变，可引起炎性因子释放减少、抗炎因子产生增加，并导致特定信号通路（如P13K通路）和负性调节因子（如SHIP1、SOCS、FLN29等）的激活。除此之外，TLR2通路、Gi蛋白、蛋白激酶C（protein kinase C，PKC）以及一些信号分子的剪接异构体等也参与了内毒素耐受现象的发生。总之，内毒素耐受是一个由多种原因引起的、多种生物物质参与的复杂病理生理过程，是机体抵抗G-细菌感染的重要保护机制。因此，探索内毒素耐受的机制，寻求机体内源性的抗炎机制将为败血症等一些致死性感染性疾病的治疗提供新的思路和理论依据。

英文摘要：

Endotoxin tolerance has been attacted for more than 50 years, but so far its molecular mechanisms remain to be resolved. TLR4, the major receptor for LPS, was tbund to be involved in LPS signaling transduction and to have a close relationship with endotoxin tolerance. Quantitative, structural and functional changes of receptors, adaptor proteins and transcription factors in TLR4 signaling pathways might have effects on the decrease in proinflammatory cytokines,increase in anti-inflammatory cytokines and activation of special signaling pathways （such as PI3K pathways）as well as some negative regulation factors （SHIP1,SOCS, FLN29, et al） during the development of endotoxin tolerance. Furthermore, TLR2, Gi protein, PKC and several selective splicing isoforms are involved in endotoxin tolerance. So endotoxin tolerance is a complicated pathophysiological process caused by diverse reasons and involved in many biological substances. It is also an important protective mechanism of human body infected with G- bacteria. Exploring the mechanism of endotoxin tolerance, seeking endogenous protective mechanism of human body would provide new theory and new ways to overcome series of fatal infective diseases including sepsis.