抗体介导排斥反应（AMR）是肝移植术后困扰临床医生的主要问题，且机制不明影响预后。已有研究表明，移植受者体内针对供者的特异性抗体(DSA)是AMR发生的原因，内皮细胞是AMR的主要靶细胞，抗体可介导内皮细胞损伤，同时，P-选择素在内皮细胞凋亡中起重要作用。我们前期研究发现HLA相合肝移植术后排斥发生少，ASK1-JNK信号通路是内皮细胞凋亡的主要机制，这提示HLA抗体有可能介导P-选择素-ASK1-JNK内皮细胞凋亡途径。本项目拟通过检测抗HLAIgG3介导的供者内皮细胞P-选择素的表达，观察激活的单核细胞释放ICAM-1和β2整合素的表达水平，证实HLAIgG3通过诱导内皮细胞表达P-选择素，促进单核细胞粘附，最终介导ASK1-JNK信号通路致内皮细胞凋亡，启动AMR过程。本研究可望深入阐明DSA结合内皮细胞引起AMR的机制，为肝移植术后排斥反应的防治提供新的靶点和临床干预手段。

Antibody-mediated rejection (AMR), also known as humoral rejection after liver transplant is a major problem plagued clinicians, whose mechanism remainsis unknown, affecting the prognosis. Previous studies indicate transplant donor-specific antibody (DSA) is the cause of AMR,which mainly target endothelial cells. Antibodies may mediate endothelial cell injury, also P-selectin plays an important role in endothelial cell apoptosis. Our previous data showed HLA-identical induced less acute rejection post liver transplant, ASK1-JNK signaling is a major pathway of endothelial cell apoptosis, suggesting that HLA antibodies may mediate P-selectin-ASK1-JNK pathway apoptosis of endothelial cells. Based on these data, we propose HLAIgG3 may induce P-selectin expression in endothelial cells, which bind with monocytes surface PSGL-1 mediate monocytes activation by using static adhesion assay, resulting in high level expression of intercellular adhesion molecule-1 (ICAM-1) and β2- integrin. This activation ultimately induce ASK1-JNK signaling in endothelial cell, resulting in endothelial cells apoptosis, thereby initiating AMR process. The study is expected to further elucidate the mechanism of antibody induced AMR through endothelial cells apoptosis and provides a new target for clinical prevention and intervention for rejection post liver transplant.