Role of the innate immune system in animal models of living donor liver transplantation

在活体供体肝移植（LDLT）中，先天免疫系统分别在调节残肝的再生和移植以及破坏移植中的炎症过程（如缺血/再灌注损伤、排斥反应、感染）中发挥重要作用。由于有研究表明toll样受体(TLR)-系统可能对这些事件至关重要，我们想研究它在LDLT中的作用，TLR 1-9激动剂将被测试其诱导或抑制促或抗再生细胞因子和信号分子的能力。和non-parenchyma !肝细胞。在大鼠LDLT模型中，在肝切除或移植前分别用TLR激动剂对供体和受体进行预处理，并在术后评估临床结果、组织学、生化和分子变化。为了研究Kupffer细胞是否参与任何tlr介导的效应，这些实验在有或没有gdcl预处理的情况下进行。最后，我们将利用IRF-3和MyD88敲除小鼠进一步研究tlr介导的信号通路在部分肝切除后的作用。最终，这些实验旨在通过靶向调节tlr系统来改善LDLT的临床结果。

In living donor liver transplantation (LDLT), the innate immune system plays an important role in regulating the regeneration of the remnant liver and the transplant as well as damaging inflammatory processes (e.g., ischemia/reperfusion injury, rejection, infections) in the transplant, respectively. Since it has been suggested that the Toll-Like-Receptor (TLR)- system may be crucial for these events, we would like to investigate its role in LDLT, TLR 1-9 agonists will be tested for their ability to induce or suppress pro- or anti-regenerative cytokines and signaling molecules in isolated parenchyma! and non-parenchyma! liver cells. In a rat model of LDLT, donor and recipient are pretreated with TLR agonists before liver resection or transplantation, respectively, and clinical outcome, histological, biochemical and molecular changes are assessed postoperatively. To investigate if Kupffer cells are involved in any TLR-mediated effects these experiments are performed with or without GdClpretreatment. Finally, IRF-3 and MyD88 knockout mice will be used to further investigate the role of the TLR-mediated signaling pathways after partial liver resection. Ultimately, these experiments are aimed improving the clinical outcome of LDLT by targeted modulation of the TLR-system.