THE ROLE OF GENDER ON GUT AND GUT-INDUCED LUNG INJURY

性别对肠道和肠道引起的肺损伤的作用

• 批准号: 7074169
• 负责人: EDWIN A DEITCH
• 金额: $ 8.29万
• 依托单位: UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7074169
• 关键词: cytoprotection; disease /disorder proneness /risk; estrogens; gastrointestinal circulation; gender difference; hemorrhagic shock; hormone regulation /control mechanism; injury; intestines; ischemia; laboratory rat; lung injury; lymphatic circulation; lymphatic system; membrane permeability; mesentery; nitric oxide synthase; pathologic process; portal vein; septicemia; sex hormones; testosterone; trauma; vascular endothelium

Trauma is the leading cause of death in people under the age of 40 and MODS is the leading cause of death in trauma patients surviving the initial 72 hour injury period. In fact, MODS is the leading cause of death in ICUs today. Although still somewhat controversial, there is recent evidence that the response to injury and sepsis may differ between males and females, with females being more resistant to the adverse consequences of T/HS than males. Thus, understanding the mechanisms by which trauma-hemorrhagic shock (T/HS) leads to MODS, as well as the role of sex hormones in modulating this response, is of major health importance. This Project will follow up on our results indicating that male, but not female, rats develop T/HS-induced lung injury and endothelial cell activation/injury by testing the following two hypotheses. The first hypothesis is that T/HS-induced lung injury and increased endothelial cell permeability is secondary to gut injury and is mediated by factors exiting the gut via the mesenteric lymphatics but not the portal vein. The second hypothesis is that sex hormones modulate gut and hence distant organ injury in a model of T/HS. To test these hypotheses, we will first investigate the potential mechanisms of why the female gut is more resistant than the male gut to T/HS-induced gut injury and does not produce toxic lymph. Next, we will investigate the role of sex hormones as modulators of resistance and susceptibility to T/HS-induced gut and lung injury. We will investigate the hypothesis that estrogen protects against T/HS-induced gut injury by limiting iNOS induction. Lastly, we will investigate the mechanisms by which T/HS mesenteric lymph, alone or in combination with PMNs, increases vascular permeability and how this is influenced by gonadal hormonal manipulation.

创伤是40岁以下人群死亡的主要原因，而MODS是导致