肝移植术后早期移植物功能不全（EAD）发生率高，进展迅速，缺乏早期预警和靶向干预手段，严重影响移植物和受者存活。我们前期分析肝移植蛋白磷酸化谱和动态免疫谱等发现，移植物再灌注后内源性损伤相关分子HSP27磷酸化水平、TLR4表达水平升高，而移植术/再灌注后早期外周血NK细胞向肝脏募集，促进急性肝损。我们进而提出假设：移植肝组织再灌注后HSP27发生磷酸化和胞外分泌，启动“损伤分子识别模式”活化TLR4通路，诱导NK细胞响应和下游炎症级联反应，最终导致肝移植术后EAD发生。本项目拟通过小鼠肝移植和再灌注损伤模型、临床肝移植样本动态监测等手段分析p-HSP27/TLR4通路与NK细胞间的交互关系，研究HSP27磷酸化诱导EAD发生的分子机制，以及其对术后EAD的早期预警效能。本研究旨在揭示移植肝再灌注后向EAD进展的关键分子生物学模式，鉴定肝移植术后EAD的干预靶点和早期预警分子标记物。

The incidence of early allograft dysfunction (EAD) after liver transplantation is very high. EAD develops quite fast, and there are no efficient therapeutic and prognostic strategies for EAD. Therefore, EAD adversely affects the graft and recipient survival. We previously performed dynamic protein phosphorylation profiling and immune spectrum profiling for liver transplantation, and found increased phosphorylation of HSP27 and TLR4 expression after reperfusion of the liver graft. Meanwhile, we observed the recruitment of NK cells into the liver graft after transplantation or reperfusion, which can cause further acute injury in the liver. Therefore, we assume that phosphorylation and secretion of HSP27 after reperfusion of the liver tissues will initiate the “Damage-related molecular pattern” and activate TLR4 signaling pathway, and then recruit and activate NK cells with subsequent inflammatory reaction in the liver graft, which finally causes EAD. Here we will focus on the regulation effect of p-HSP27 on TLR4 signaling and NK cell activation through mouse liver transplantation and reperfusion model and clinical transplant sample monitoring et al., so as to study the role of HSP27 phosphorylation in EAD and its predicting capacity for EAD in the early phase. The study aims to clarify the biological pattern of EAD, and identify the therapeutic target and early-phase biomarker for EAD after liver transplantation.