脑死亡供肝肝移植缺血再灌注损伤（IRI）的具体机制未明。凝血酶能通过其受体(PAR1)激活内皮细胞的促炎反应。CARMA3-Bcl10-MALT1信号转导体能介导G蛋白偶联膜受体激活NF-κB促炎信号。我们前期研究发现大鼠脑死亡后凝血酶激活，拮抗PAR1可以抑制脑死亡大鼠肝窦内皮细胞中CARMA3、ICAM-1和MCP-1蛋白表达上调及p65核转位，并减轻肝组织中炎性细胞浸润。据此推测脑死亡供肝中存在凝血酶通过PAR1调控肝窦内皮细胞CARMA3信号转导体激活NF-κB信号，促进移植术后IRI的发生。为此，本课题拟通过基因敲除、RNA干扰、免疫共沉淀、激光共聚焦等技术，从体内体外层面观测凝血酶、PAR1、炎性细胞及相关分子、组织病理、肝酶学指标等变化，探索该信号通路在脑死亡供肝移植术后IRI的作用，为提高脑死亡供肝质量并减轻移植术后IRI提供新的思路和可能的防治方法。

Brain death has aggravated the ischemia reperfusion injury in liver transplantation with graft donation after brain death, and its mechanism has not been fully clarified. Thrombin can activate endothelial cells to promote the inflammatory reaction through its receptor (PAR1). CARMA3, Bcl10 and MALT1 combined together, transduct proinflammatory signal from G protein coupled membrane receptor to NF-kappa B. Our previous study found that thrombin activation after brain death, antagonizing PAR1 could inhibit carma3, ICAM-1 and MCP-1 protein expression and p65 nuclear translocation in the liver sinusoidal endothelial cells of brian death rats, and reduce the infiltration of inflammatory cells in the liver tissue. We speculated that the signal pathway of thrombin-PAR1 in the liver sinusoidal endothelial cell could activate the NFkappa B signal to promote ischemia reperfusion injury in liver transplantation with graft donation after brain death through CARMA3 signal transduction. For further confirmation, this paper intends to through gene knock-out, RNA interference and immune coprecipitation, laser confocal and technology, observe thrombin and PAR-1 and inflammatory cells and molecules, histopathologic changes,.ALT and AST etc in vitro and in vivo, and explore the signaling pathway for ischemia reperfusion injury of liver transplantation with graft donation after brain death, in order to provide new thoughts and methods of prevention and treatment for improving the liver quality of brain death donor and reducing ischemia reperfusion injury of liver transplantation with graft donation after brain death.