缺血后处理对边缘性供肝的影响及HMGB1在其中的作用机制研究

项目名称： 缺血后处理对边缘性供肝的影响及HMGB1在其中的作用机制研究

项目编号： No.81200330

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学一处

项目作者： 王楠

作者单位： 中国人民解放军第四军医大学

项目金额： 24万元

中文摘要： 以脂肪肝为主的边缘性供肝扩大了供肝来源，但增加了术后早期移植肝功能不良和原发性移植肝无功能的风险，而脂肪肝对缺血再灌注损伤（IRI）的高易感性被认为是其主要原因。脂肪肝移植IRI的具体机制尚不明了，并缺乏有效的保护方法；研究表明高迁移率族蛋白-1（HMGB1）在机体损伤后免疫反应中发挥重要的调节作用，是IRI中关键的早期炎症反应介质，但在脂肪肝移植IRI中的作用尚无研究。本课题组在前期研究中发现，缺血后处理（IPostC）能够显著减轻正常供肝移植后的IRI。本项目通过建立大鼠脂肪肝移植模型，检测不同脂肪变性程度供肝与移植后IRI程度和HMGB1表达水平的相关性，观察IPostC对脂肪供肝移植后IRI是否具有保护作用，并通过特异性增强和抑制HMGB1，研究HMGB1在脂肪肝移植后IRI中的作用，揭示IPostC影响脂肪供肝移植后IRI的分子机制，为减轻边缘性供肝移植后的IRI提供新的途径。

中文关键词： 肝移植；脂肪肝；缺血再灌注损伤；缺血后处理；高迁移率族蛋白-1

英文摘要： The only effective method to treat liver disease in final stage is liver transplantation. Due to lack of donor, more and more margin liver donors were adopted, especially fatty liver donors. Fatty donor livers expand the source of donor liver graft, but increase the risk of poor early graft function (PEGF) and primary non-function (PNF) on liver allograft. Hepatic ischemia reperfusion (IR) injury is a common pathological process of liver transplantation, which is considered as the primary cause of PEGF and PNF. Therefore, it is of great interest to elucidate the underlying pathomechanisms and to develop protective strategies for attenuating the IR injury of the margin donor livers. High mobility group box-1 (HMGB1) is a capital mediator in the early inflammatory reaction after IR injury, and it exerts important accommodation function in the priming and developing process of immune reaction after injury. The effect of HMGB1 in the IR injury after fatty liver transplantation is still not studied. Ischemic postconditioning (IPostC), which consists of several very short circles of ischemia and reperfusion applied immediately at the onset of reperfusion, offers an attractive and amenable approach to organism protection. In our early study, we found IPostC could attenuate IR injury in orthotopic liver transplantation

英文关键词： liver transplantation；steatotic liver；ischemia reperfusion injury；ischemic postconditioning；high mobility group box-1