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

多发性创伤诱导复杂的分子和细胞危险反应。尽管使用了现代治疗策略，但这种反应在临床过程中经常会导致严重的创伤后并发症（脓毒症、多器官功能障碍综合征、死亡）。特别是Toll样受体（TLR）和补体系统参与病原体和受损组织的识别和消除。虽然多发性创伤后早期阶段（<24小时）的病理生理学和免疫学后果已在几项临床和实验研究中进行了研究，但没有长期的大型动物模型，其中形态和功能后果以及分子危险反应可以在临床相关环境中进行研究。长期的大型动物模型似乎也是评估新的治疗策略不可或缺的。因此，我们旨在研究不同手术策略（股骨髓内钉和肝破裂手术控制vs外固定器和肝脏填塞）以及免疫控制与C5和CD 14的平行阻断在建立的猪多发性创伤模型中的影响，该模型具有标准化组织损伤和出血性休克以及指导重症监护治疗。此外，将阐明微泡的局部和系统表达模式，包括miRNA的起源和内容。也将研究miRNA的靶基因。作为一个未来的观点，新的诊断和治疗方法的治疗多发性创伤患者的细胞和器官功能的改善和连续更高的生存率可能会被开发。

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.