Resveratrol as an adjunct to resuscitation fluid following hemorrhage injury

白藜芦醇作为失血性损伤后复苏液的辅助剂

• 批准号: 8825553
• 负责人: Raghavan Pillai Raju
• 金额: $ 18.01万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8825553
• 关键词: Resveratrol; adjunct; resuscitation; fluid; following

DESCRIPTION (provided by applicant): Severe hemorrhage causes whole body hypoxia, multiple organ dysfunction and death. Fluid resuscitation is employed to restore organ perfusion and reoxygenation following hemorrhagic injury. Reoxygenation causes oxidative damage and cell and organ injury and there is a need to develop better resuscitation methods to reduce cell injury following hemorrhage. Our systematic study of mitochondrial functional genomics in the rat resulted in the identification of a novel pathway involving Sirt1 (mammalian homolog of sir2-silent mating type information regulation 2) in hemorrhagic injury. Our studies demonstrated a significant decline in Sirt1 expression following trauma-hemorrhage (T- H). Our preliminary data also indicate that resveratrol (trans-3,5,4'-trihydroxystilbene), a phytoalexin antioxidant found i grapes, and an enhancer of Sirt1 activity, reduces heart and liver injury following hemorrhage. Our objective is therefore to establish that resveratrol can be used as an adjunct to resuscitation fluid, following hemorrhage. We will also determine the molecular basis of tissue injury and resveratrol-mediated protection following T-H. Our hypothesis is that resveratrol reduces organ injury following hemorrhagic shock and therefore it can be used as an adjunct to resuscitation fluid. We will test the central hypothesis by pursuing the following four Specific Aims: (1) optimize the time and dose of resveratrol as an adjunct to resuscitation fluid, (2) determine the effect of resveratrol treatment on cellular energetics following T-H in the heart and the liver, (3 identify the mediators and mechanism of T-H injury resolution by resveratrol and (4) establish that resveratrol reduces organ injury and improve survival following T-H. We will use state-of-the-art tools and techniques such as mitochondrial functional genomics and ChIP-chip method to test the hypothesis. When the proposed studies are completed, in addition to identifying resveratrol as an adjunct to resuscitation fluid, we would have also gained new knowledge on molecular pathways involved in hemorrhage injury and their modulation by the antioxidant resveratrol.

描述（由申请人提供）：严重的出血会导致全身缺氧，多器官功能障碍和死亡。流体复苏用于恢复出血性损伤后的器官灌注和重氧。重氧会导致氧化损伤，细胞和器官损伤，并且有必要开发出更好的复苏方法来减少出血后细胞损伤。我们对大鼠线粒体功能基因组学的系统研究导致鉴定出涉及SIRT1的新途径（siR2-SiR2-SiLent交配类型信息调节2）中的新途径。我们的研究表明，创伤性突出（T- H）后SIRT1表达显着下降。我们的初步数据还表明，白藜芦醇（Trans-3,5,4'-Trihydroxystilbene），一种植物甲状腺素抗氧化剂发现了I葡萄和SIRT1活性的增强剂，可减少出血后心脏和肝损伤。因此，我们的目标是确定白藜芦醇可以用作复苏的辅助 流体，出血后。我们还将确定T-H后组织损伤和白藜芦醇介导的保护的分子基础。我们的假设是，白藜芦醇在出血性休克后减少器官损伤，因此可以用作复苏液的辅助。我们将通过追求以下四个特定目的来检验中心假设：（1）优化白藜芦醇作为复苏液的辅助性的时间和剂量，（2）确定白藜芦醇治疗对T-H心脏和肝脏T-H后T-H的细胞能量的影响，（3确定了通过TH Hubine and Insuptors and Inderiators and Inderiators and Intery Ornuption and Intrucient and corner and restor and corverrol and Resatr and coratr and resatr和4）（4）（4）（4）（4）（4）（4）（4）（4）（4）（4）（4）（4）（4）（4）（4）4）在T-H之后，我们将使用最先进的工具和技术，例如线粒体功能基因组学和芯片芯片方法来测试拟议的研究，除了将白藜芦醇作为恢复流体的辅助性外，我们还将通过分子途径获得新知识。