Kohut Lauryn K, Darwiche Sophie S, Brumfield John M, Frank Alicia M, Billiar Timothy R
Department of Surgery, University of Pittsburgh, USA.
J Vis Exp. 2011 Jun 6(52):2068. doi: 10.3791/2068.
It is common knowledge that severe blood loss and traumatic injury can lead to a cascade of detrimental signaling events often resulting in mortality. These signaling events can also lead to sepsis and/or multiple organ dysfunction (MOD). It is critical then to investigate the causes of suppressed immune function and detrimental signaling cascades in order to develop more effective ways to help patients who suffer from traumatic injuries. This fixed pressure Hemorrhagic Shock (HS) procedure, although technically challenging, is an excellent resource for investigation of these pathophysiologic conditions. Advances in the assessment of biological systems, i.e. Systems Biology have enabled the scientific community to further understand complex physiologic networks and cellular communication patterns. (14) Hemorrhagic Shock has proven to be a vital tool for unveiling these cellular communication patterns as they relate to immune function. This procedure can be mastered! This procedure can also be used as either a fixed volume or fixed pressure approach. We adapted this technique in the murine model to enhance research in innate and adaptive immune function. Due to their small size HS in mice presents unique challenges. However due to the many available mouse strains, this species represents an unparalleled resource for the study of the biologic responses. The HS model is an important model for studying cellular communication patterns and the responses of systems such as hormonal and inflammatory mediator systems, and danger signals, i.e. DAMP and PAMP upregulation as it elicits distinct responses that differ from other forms of shock. The development of transgenic murine strains and the induction of biologic agents to inhibit specific signaling have presented valuable opportunities to further elucidate our understanding of the up and down regulation of signal transduction after severe blood loss, i.e. HS and trauma. There are numerous resuscitation methods (R) in association with HS and trauma. A fixed volume resuscitation method of solely lactated ringer solution (LR), equal to three times the shed blood volume, is used in this model to study endogenous mechanisms such as remote organ injury and systemic inflammation. This method of resuscitation is proven to be effective in evaluating the effects of HS and trauma.
众所周知，严重失血和创伤性损伤会引发一系列有害的信号事件，常常导致死亡。这些信号事件还会导致败血症和/或多器官功能障碍（MOD）。因此，研究免疫功能抑制和有害信号级联反应的原因，对于开发更有效的方法来帮助创伤患者至关重要。这种固定压力失血性休克（HS）程序虽然在技术上具有挑战性，但却是研究这些病理生理状况的绝佳资源。生物系统评估的进展，即系统生物学，使科学界能够进一步了解复杂的生理网络和细胞通讯模式。（14）失血性休克已被证明是揭示这些与免疫功能相关的细胞通讯模式的重要工具。这个程序是可以掌握的！这个程序也可以用作固定容量或固定压力方法。我们在小鼠模型中采用了这种技术，以加强对先天性和适应性免疫功能的研究。由于小鼠体型小，HS在小鼠中存在独特的挑战。然而，由于有许多可用鼠种，该物种是研究生物学反应的无与伦比的资源。HS模型是研究细胞通讯模式以及激素和炎症介质系统等系统反应以及危险信号（即损伤相关分子模式和病原体相关分子模式上调）的重要模型，因为它引发的独特反应与其他形式的休克不同。转基因小鼠品系的开发以及诱导生物制剂抑制特定信号传导，为进一步阐明我们对严重失血（即HS和创伤）后信号转导上调和下调的理解提供了宝贵机会。与HS和创伤相关的复苏方法（R）有很多。在这个模型中，使用仅含乳酸林格氏液（LR）的固定容量复苏方法，其等于失血量的三倍，以研究诸如远程器官损伤和全身炎症等内源性机制。这种复苏方法已被证明在评估HS和创伤的影响方面是有效的。
