Ischemia and reperfusion injury in liver transplantation
Ischemia and reperfusion injury in liver transplantation
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DOI：
10.1016/j.transproceed.2005.03.134
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发表时间：
2005-05-01
影响因子：
0.9
通讯作者：
Busuttil, RW
中科院分区：
文献类型：
--
作者：
Kupiec-Weglinski, JW;Busuttil, RW
肝缺血再灌注（I/R）损伤是影响肝移植功能的多因素过程。了解I/R损伤的机制对于设计改善肝移植预后的治疗策略至关重要。再氧化后活性氧的产生会造成组织损伤，并引发细胞级联反应，导致炎症、细胞死亡和最终的器官衰竭。越来越多的证据表明，Kupffer细胞和T细胞介导了中性粒细胞炎症反应的激活。活化的中性粒细胞浸润损伤的肝脏，同时内皮细胞粘附分子表达增加。血红素加氧酶（HO）系统是细胞应激过程中激活的最关键的细胞保护机制之一，发挥抗氧化和抗炎功能，调节细胞周期，维持微循环。Kupffer细胞上toll样受体（TLR）的激活可能为I/R损伤序列中的促炎反应提供触发信号。事实上，解剖TLR下游信号通路在探索基于肝I/R损伤代表宿主“先天”免疫的概念的新治疗策略中起着重要作用。
Ischemia/reperfusion (I/R) injury is a multifactorial process detrimental to liver graft function. An understanding of the mechanisms involved in I/R injury is essential for the design of therapeutic strategies to improve the outcome of liver transplantation. The generation of reactive oxygen species subsequent to reoxygenation inflicts tissue damage and initiates a cellular cascade leading to inflammation, cell death, and ultimate organ failure. The accruing evidence suggests that Kupffer cells and T cells mediate the activation of neutrophil inflammatory responses. Activated neutrophils infiltrate the injured liver in parallel with increased expression of adhesion molecules on endothelial cells. The heme oxygenase (HO) system is among the most critical of the cytoprotective mechanisms activated during the cellular stress, exerting antioxidant and anti-inflammatory functions, modulating the cell cycle, and maintaining the microcirculation. The activation of toll-like receptors (TLR) on Kupffer cells may provide the triggering signal for pro-inflammatory responses in the I/R injury sequence. Indeed, dissecting TLR downstream signaling pathways plays a fundamental role in exploring novel therapeutic strategies based on the concept that hepatic I/R injury represents a case for host "innate" immunity.