MOLECULAR BIOLOGY OF HEMORRHAGIC SHOCK

在这个国家，创伤是人们在战争中死亡的主要原因。 年龄44岁。严重头部损伤后，出血及其后果 是这些年轻人发病和死亡的最重要原因， 健康的个体。该中心赠款提案旨在推动 我们对导致器官损伤的分子机制的理解， 功能障碍的最严重形式的出血性损伤。通过研究 器官损伤的迅速发生，这是严重的 失血性休克私家侦探将排除其他延迟发病原因 例如通常在创伤受害者中遇到由于感染引起的脓毒症 还有其他重症患者。换句话说，P.I. 认为组织损伤和器官衰竭的病理生理学 与失血性休克相关的是一个知之甚少的复杂的 这是一个值得重点和详细研究的过程。此外，更好的 了解这种疾病的过程将导致更有效的 治疗策略。 私家侦探提出了理解器官损伤的关键之一 出血性休克导致的是表征分子事件 导致引发和促进炎症变化， 失血性休克大多数以前的研究都研究了 休克加复苏对炎症和器官损伤参数的影响。 与以前的方法相比，P.I.将分子 失血性休克事件分为三个不同的阶段：休克 阶段、复苏阶段和复苏后阶段。私家侦探 假设在每一个细胞中基因表达都有特定的变化， 由冲击单独的影响或后果引起的阶段 休克后的复苏这些诱导基因表达的变化 促进炎症和器官损伤。私家侦探假设， 休克阶段的持续时间和严重程度决定了 表型变化以及炎症反应的强度 复苏后。私家侦探还提出， 宿主对随后的炎症损伤的耐受性通过基因改变而增强， 休克和复苏阶段引起的表达， 这种增强的脆弱性阻止了炎症的解决， 反应

Trauma is the leading cause of death In this country in people under the age of 44 years. After major head injury, hemorrhage and its consequences are the most important causes of morbidity and mortality in these young, otherwise healthy individuals. This Center Grant proposal seeks to advance our understanding of the molecular mechanisms leading to organ injury and dysfunction in the severest forms of the hemorrhagic insult. By studying the rapid onset of organ injury, which is characteristic of severe hemorrhagic shock, the P.I. will exclude other delayed causes of morbidity such as sepsis due to infection, commonly encountered in trauma victims but also other critically ill patients. Stated another way, the P.I. believes the pathophysiology of the tissue injury and organ failure associated with hemorrhagic shock alone is a poorly understood and complex process that warrants focused and detailed study. Furthermore, a better understanding of this disease process will lead to more effective treatment strategies. The P.I. proposes that one of the keys to understanding organ injury resulting from hemorrhagic shock is to characterize the molecular events leading to the initiation and promotion of inflammatory changes in hemorrhagic shock. Most previous studies have examined the net effect of shock plus resuscitation on parameters of inflammation and organ damage. In contrast to these previous approaches, the P.I. divides the molecular events of the hemorrhagic shock into three distinct phases: the shock phase, the resuscitation phase, and the post-resuscitation phase. The P.I. hypothesizes that there are specific changes in gene expression in each phase that are induced by the effects of shock alone or the consequences of resuscitation following shock. These induced changes in gene expression promote inflammation and organ injury. The P.I. postulates that the duration and severity of the shock phase determine the degree of phenotypic changes and hence the intensity of the inflammatory response following resuscitation. The P.I. also proposes that the susceptibility of the host to subsequent inflammatory insults is enhanced by changes in gene expression resulting from the shock and resuscitation phases, and that this enhanced vulnerability prevents the resolution of the inflammatory response.