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

先天免疫系统在活体肝移植动物模型中的作用

• 批准号: 28074726
• 负责人: Professor Dr. Jörg Friedrich Schlaak
• 金额: --
• 依托单位: Klinik für Gastroenterologie und Hepatologie
• 依托单位国家: 德国
• 项目类别: Clinical Research Units
• 财政年份: 2006
• 资助国家: 德国
• 起止时间: 2005-12-31 至 2011-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/28074726?language=en
• 关键词: Role; innate; immune; system; animal

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.

在活体供肝移植（LDLT）中，先天免疫系统在调节残肝和移植物的再生以及破坏炎症过程（例如，缺血/再灌注损伤、排斥、感染）。由于已经表明Toll样受体（TLR）系统可能对这些事件至关重要，我们想研究其在LDLT中的作用，将测试TLR 1-9激动剂在分离的实质中诱导或抑制促或抗再生细胞因子和信号分子的能力！和非实质组织肝细胞在大鼠LDLT模型中，供体和受体在肝切除或移植前分别用TLR激动剂预处理，并在术后评估临床结果、组织学、生物化学和分子变化。为了研究枯否细胞是否参与任何TLR介导的作用，这些实验在有或没有GdCl预处理的情况下进行。最后，IRF-3和MyD 88敲除小鼠将用于进一步研究TLR介导的信号通路在部分肝切除术后的作用。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。

项目成果

Glycine Pretreatment Ameliorates Liver Injury After Partial Hepatectomy in the Rat

• DOI: 10.3109/08941930903469466
• 发表时间: 2010-02-01
• 期刊: JOURNAL OF INVESTIGATIVE SURGERY
• 影响因子: 1.9
• 作者: Benko, Tamas;Frede, Stilla;Rauen, Ursula
• 通讯作者: Rauen, Ursula