Role of systemic hypothermia on inflammatory response and apoptosis in severe tissue injury

全身低温对严重组织损伤炎症反应和细胞凋亡的作用

• 批准号: 5408987
• 负责人: Professorin Dr. Brigitte Vollmar
• 金额: --
• 依托单位: Institut für Klinisch-Experimentelle Chirurgie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2003
• 资助国家: 德国
• 起止时间: 2002-12-31 至 2008-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5408987?language=en
• 关键词: Role; systemic; hypothermia; inflammatory; response

Changes in body temperature occur during inflammation upon severe tissue injury, however the role of body temperature on inflammatory responses remains obscure. Thermoregulatory responses considerably vary from hypothermia to fever. Though hypothermic trauma patients seem to have a worse prognosis, there is the question whether it is the hypothermia per se or the severity of injury producing the hypothermia that is responsible for increased mortality. The proposed project focuses on how mild to moderate hypothermia modulates local and systemic inflammatory response and cell apoptosis upon tissue injury. Based on recent work of our group using the skinfold chamber model and high resolution multifluorescence microscopy in mice (FASEB J, 2002), we will assess microvascular, cellular and molecular events in severely injured tissue of p53+/+ and p53-/- mice with hypothermia (32°C-35°C), emphasising the role of low body temperature on the progress of p53-mediated apoptotic tissue death. Additionally, in vitro approaches using p53 wild-type and p53 mutant cells further allow us to study the effect of subnormal temperatures on cellular stress response. The proposed project should solve the controversy about the value of hypothermia in severe trauma, being either a simple marker of illness or a major contributor to disease.

在严重组织损伤的炎症过程中，体温会发生变化，但体温对炎症反应的作用仍不清楚。从体温过低到发烧，体温调节反应差异很大。尽管低温创伤患者的预后似乎较差，但存在的问题是体温过低本身还是导致体温过低的损伤严重程度导致了死亡率增加。该项目的重点是轻度至中度低温如何调节组织损伤时的局部和全身炎症反应和细胞凋亡。基于我们小组最近使用小鼠皮褶室模型和高分辨率多荧光显微镜的工作（FASEB J，2002），我们将评估低温（32°C-35°C）的p53+/+和p53-/-小鼠严重损伤组织中的微血管、细胞和分子事件，强调低体温对p53介导的进展的作用 凋亡组织死亡。此外，使用 p53 野生型和 p53 突变细胞的体外方法进一步使我们能够研究低于正常温度对细胞应激反应的影响。拟议的项目应该解决有关严重创伤中体温过低的价值的争议，体温过低要么是疾病的简单标志，要么是疾病的主要促成因素。