Differential surgical and immunological control in a long-term pig polytrauma model

多重创伤会引起复杂的分子和细胞危险反应。尽管使用了现代治疗策略，这种反应在临床过程中经常会导致严重的创伤后并发症(败血症、多器官功能障碍综合征、死亡)。尤其是Toll样受体(TLR)和补体系统参与识别和消除病原体和受损组织。虽然多发伤早期(24小时)的病理生理学和免疫学后果已经在一些临床和实验研究中得到了研究，但还没有长期的大型动物模型，可以在临床相关的环境中研究形态和功能的后果以及分子危险反应。对于评估新的治疗策略，长期的大型动物模型似乎也是不可或缺的。因此，我们旨在研究不同的手术策略(股骨髓内钉、肝破裂的手术控制与外固定器和肝填塞)以及免疫控制(同时阻断C5和CD14)对猪多发伤模型的影响，建立标准化的组织损伤和失血性休克，并指导重症监护治疗。此外，还将阐明微囊的局部和系统表达模式，包括miRNAs的来源和内容。还将研究miRNA的目标基因。作为未来的展望，多发性创伤患者的新的诊断和治疗方法可能会被开发出来，以改善细胞和器官功能，并持续提高存活率。

Multiple trauma induces a complex molecular and cellular danger response. Despite the use of modern treatment strategies, this response can regularly results in severe posttraumatic complications (sepsis, multiple organ dysfunction syndrome, death) over the clinical course. Particularly Toll-like receptors (TLR) and the complement system are involved in the recognition and elimination of pathogens and damaged tissue. While the pathophysiology and immunologic consequences in the early phase after multiple trauma (<24 h) have been investigated in several clinical and experimental studies, there is no long-term large animal model, in which morphological and functional consequences as well as the molecular danger response can be investigated in a clinically relevant setting. Long-term large animal models also seem to be indispensable for the evaluation of new therapeutic strategies. Therefore, we aim to investigate the influence of different surgical strategies (intramedullary femur nail & surgical control of liver rupture vs external fixator & liverpacking) as well as immune control with a parallel blockade of C5 and CD14 in an established porcine multiple trauma model with standardized tissue damage and hemorrhagic shock and guideline directed intensive care therapy. In addition, local and systemic expression patterns of microvesicles concerning origin and content including miRNAs will be elucidated. Target genes for miRNA will be also investigated. As a future perspective, new diagnostic and therapeutic approaches for the treatment of the multiple trauma patient with improvements of cellular and organ function and a consecutively higher survival might be developed.