机体脑死亡后常见循环功能不稳定，引起肝脏低灌注，肝细胞缺氧，是导致肝功能受损的重要原因。体外膜肺氧合（ECMO）保证有效的氧合灌注。我们临床上率先应用ECMO于循环不稳定的脑死亡供体，并建立了应用标准，取得了明显的肝功能保护和修复效果。前期工作证实，循环不稳定的脑死亡供体经ECMO灌注后，活性氧(ROS)水平降低，同时存在肝细胞的自噬与凋亡。自噬是否在ECMO保护肝细胞功能过程中扮演重要角色？本课题拟建立三个研究对象：①临床上遵循标准的循环不稳定的脑死亡供体，应用ECMO；②脑死亡后休克大鼠模型，应用ECMO；③体外肝实质细胞ROS干预模型。通过检测ROS介导的自噬活化MAPK-JNK-Benclin/Atg4和自噬抑制PI3K-AKT-mTOR信号通路，探讨ECMO作用于循环不稳定脑死亡供体肝细胞的自噬分子作用及机制，为临床应用ECMO保护循环不稳定脑死亡供体肝脏功能提供新的理论依据。

Unstable circulation always occurs in 25~80% the brain dead donor, it can cause the liver blood low perfusion and then hepatocyte oxygen defliciency,which is the most important reason for the damage of liver function. .In China, the liver function of the brain dead donor with unstable circulation was first to maintained by extracorporeal membrane oxygenation (ECMO). The first guideline of DBD with ECMO maintenance were written by our group. But the mechanisms are unknown. Our previous study found that the level of reactive oxygen species (ROS) of brain dead donor with unstable circulation is decreased by ECMO maintenance. the levels of ALT and AST has same changes and autophagy and apoptosis existed in these livers. So the research system included the brain dead donor with unstable circulation, the shock- dopamine-brain death model of rat and the hepatic cell model intervened ROS. In these research, the mechanisms of the liver function of the brain dead donor with unstable circulation were elucidated and investigated. The hypothesis as fellow: In the procedure of DBD with ECMO maintenance, the ROS level is reduced and the low level ROS of hepatic cell can activate the protective autophagy to inhibit the apoptosis, and include the inhibitory pathway PI3K— AKT—mTOR and activation pathway MAPK—JNK—Benclin/Atg4. It can be provided the foundation of ECMO application for maintenance of DBD.