DCD供体内不稳定血流灌注通过铁死亡途径损害供肝质量的研究

公民逝世后器官捐献(DCD)已成为最重要的供器官来源。即使按现有临床标准严格筛选，DCD供肝早期移植物功能不全的发生率也高于活体供肝。不同于活体供体，绝大多数DCD供体在救治过程中会发生频繁大幅血压波动，后果是器官血流灌注极不稳定。铁超载是铁死亡的早期事件。我们前期发现DCD器官不稳定血流灌注与铁超载密切相关，铁死亡事件相关分子与DCD供肝移植时缺血损伤程度及术后肝功能恢复密切相关。我们推测供肝不稳定血流灌注状态是以肝细胞铁死亡为主要特征，通过加重移植时的缺血再灌注损伤(IRI)进而影响肝移植预后。本研究将首先在临床DCD样本中证实肝细胞铁死亡及其与移植时IRI的相关性，进而在大型非人灵长类动物心肺复苏模型中观察肝细胞铁死亡的动态进程，探讨肝细胞铁死亡能否成为DCD供肝质量评估指标，以及干预铁死亡进程是否能改善DCD供肝质量。

Donation after citizen death (DCD) has become the most important source of donors. The incidence of early graft dysfunction of DCD donor livers was higher than that of living donor livers, even under the strict clinical criteria. Unlike living donors, the most important feature of DCD donors is that there are frequent and large blood pressure fluctuations during treatment, with the consequence that organ blood perfusion is extremely unstable. Iron overload is an early event of ferroptosis. We found that the unstable perfusion of DCD organs is closely related to iron overload, and the related molecules of ferroptosis are closely related to the degree of ischemic injury and the recovery of liver function after DCD liver transplantation. We speculate that the main feature of unstable blood flow perfusion in donor liver is the ferroptosis in hepatocytes, which may affect the prognosis of liver transplantation by aggravating the ischemia-reperfusion injury (IRI) during transplantation. This study will first confirm the relationship between ferroptosis of hepatocytes and IRI during transplantation in clinical DCD samples, and then observe the dynamic process of ferroptosis of hepatocytes in cardiopulmonary resuscitation model of large non-human primates, to explore whether ferroptosis of hepatocytes can be used as a quality evaluation index of DCD liver, and whether intervention in process of ferroptosis can improve the quality of DCD liver.