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岁以下的人的主要死因，mod是 创伤患者的死亡人数在最初的72小时受伤期内存活。实际上，mod是 今天的ICU死亡。尽管仍然有些争议，但最近有证据表明 男性和女性之间的损伤和败血症可能有所不同，女性对不利的耐药性更具 T/HS的后果比男性的后果。因此，了解创伤性造成的机制 冲击（T/HS）导致mod以及性激素在调节这种反应中的作用 健康重要性。该项目将跟进我们的结果，表明雄性但不是女性的老鼠 通过测试以下两个 假设。第一个假设是T/HS诱导的肺损伤和内皮细胞增加 渗透性继发于肠道损伤，并由通过肠系膜退出肠道的因素介导 淋巴管，而不是门静脉。第二个假设是性激素调节肠道，因此 T/HS模型中的远处器官损伤。为了检验这些假设，我们将首先研究潜力 为什么雌性肠道比男性肠道更具抗性的机制 不产生有毒淋巴。接下来，我们将调查性激素的作用 抗T/HS诱导的肠道损伤的耐药性和敏感性的调节剂。我们将 研究雌激素通过限制iNOS预防T/HS诱导的肠道损伤的假设 就职。最后，我们将研究单独或单独或中的T/HS肠系膜淋巴的机制 与PMN结合，增加血管渗透性以及如何影响性腺激素 操纵。