我们前期研究发现内毒素(LPS)触发的再灌注期Kupffer细胞(KCs)过度激活是导致肝移植缺血再灌注损害(I/RI)的重要原因之一，诱导KCs对内毒素耐受(ET)后可显著减轻I/RI。最近研究表明：LPS必须经系列的信号传递才能激活单核/巨噬细胞，调控核受体活性使众多LPS相关传导因子染色质发生改变是诱导ET建立的主要原因。NF-kB是LPS活化单核/巨噬细胞的最重要核受体之一，而富集表达于肝脏的RIP140又是调控单核/巨噬细胞NF-kB转录活性的关键性辅激活因子，抑制RIP140表达即可诱导ET。 鉴于体内80%-90%的单核/巨噬细胞是定植于肝血窦的KCs，我们提出，如能证实RIP140也是LPS诱导KCs活化的关键调控因子，那抑制RIP140表达将从调控核受体活性角度有效阻断LPS对再灌注期KCs的激活并诱导建立ET，从而为防治肝移植I/RI的基因治疗提供适宜的新靶点。

Our researches have identified that one of the most important reasons for ischemia / reperfusion injury (I/RI) after liver transplantation was the activation of Kupffer cells (KCs) triggered by LPS during reperfusion phase, and I/RI could be significantly alleviated after endotoxin tolerance (ET) induced in KCs. Macrophages activated by LPS through many sophisticated signal transduction pathways.Recent studies have demonstrated that changes on chromatin of specific LPS signal transduction proteins caused by nuclear receptors provide the major regulatory mechanisms for ET induction. NF-kB was allimportant nuclear receptors to activate macrophages caused by LPS, and receptor-interacting protein 140 (RIP140) mainly expressed in liver was one of the most important co-activator for NF-κB of macrophages. RIP140 degradation promotes ET in macrophages. As 80-90% macrophages are known as KCs located in hepatic sinusoids, we deduced that RIP140 could also play a significant role in KCs activation by LPS, and future therapeutic approaches may be targeted to supression of RIP140 gene expression to establish ET in KCs during reperfusion phase to alleviate I/RI after liver transplantation.