GENDER ROLE IN TRAUMA/HEMORRHAGE INDUCED RBC DYSFUNCTION

性别在创伤/出血引起的红细胞功能障碍中的作用

• 批准号: 7900886
• 负责人: GEORGE W MACHIEDO
• 金额: $ 15.35万
• 依托单位: UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7900886
• 关键词: Abnormal Red Blood Cell; Animals; Blood flow; Cardiovascular Diseases; Cell physiology; Cells; Clinical Research; Development; Disease; Distant; Erythrocytes; Female; Functional disorder; Gender Role; Gonadal Steroid Hormones; Hemorrhage; Human; In Vitro; Injury; Intestines; Lead; Link; Lymph; Mediating; Mesentery; Modeling; Multiple Organ Failure; Nutrient; Organ; Patients; Pilot Projects; Postmenopause; Premenopause; Rattus; Resistance; Role; Secondary to; Sepsis; Shock; Testing; Tissues; Trauma; Woman; base; in vivo; injured; male; men

Abnormal red blood cell (RBC) function, particularly decreased cell deformability, has been documented in sepsis, after trauma and during shock states. This decrease in RBC deformability is associated with, and has been shown to directly cause, impaired nutrient blood flow to various tissues, and thus might contribute to the development of the multiple organ dysfunction syndrome (MODS). However, the exact mechanisms and factors that lead to decreased RBC deformability remain to be determined. There are also studies that have documented more normal RBC deformability in women with cardiovascular disease than is seen in men with similar disease. We therefore wish to test the following two hypotheses: (1) that decreased RBC deformability after trauma-hemorrhage shock (T/HS) is secondary to gut injury and is mediated by factors carried in the intestinal lymph and; (2) that the changes in deformability following T/HS are less in females than in males. We will test the first hypothesis and investigate mechanisms by which toxic mesenteric lymph injures red cells. We propose to investigate the role of sex hormones as modulators of T/HS-induced RBC deformability in vivo. This is based on our pilot studies showing that female rats are more resistant to T/HS-induced changes in RBC deformability than male rats, as well as human studies indicating that RBC deformability is better preserved in pre-menopausal than post-menopausal women. Using in vitro studies, we propose to investigate the potential mechanisms responsible for the resistance of female rats to T/HS focusing on the role of sex hormones. Lastly, we propose to expand these animal studies to include male and female trauma patients. We believe these clinical studies will be important since they will allow us to compare the results observed in our T/HS model with those observed in trauma patients.

红细胞异常的功能（RBC）功能，尤其是细胞可变形性降低，已记录在 败血症，创伤后和冲击状态。 RBC可变形性的这种下降与 已显示出直接引起的，营养血液流向各种组织的受损，因此可能 有助于多器官功能障碍综合征（MOD）的发展。但是，确切的 导致RBC可变形性降低的机制和因素仍有待确定。有 还记录了心血管疾病女性中RBC更正常的RBC可变形性 比有类似疾病的男性所看到的。因此，我们希望检验以下两个假设：（1） 创伤性突发性休克（T/HS）后的RBC可变形性降低是肠损伤的继发性的 由肠道淋巴中携带的因子介导； （2）T/HS后的变形性变化 在女性中的少于男性。我们将检验第一个假设并研究 有毒肠系膜淋巴损伤红细胞的机制。我们建议 研究性激素作为T/HS诱导的RBC可变形性体内的调节剂的作用。这是 基于我们的试点研究，表明雌性大鼠对T/HS诱导的RBC变化具有更大的抵抗力 比男性大鼠的可变形性，以及人类研究表明RBC可变形性更好 保留在绝经前保留的比绝经后妇女保留。使用体外研究，我们 建议研究负责女性大鼠抗t/hs的潜在机制 专注于性激素的作用。最后，我们建议扩大这些动物 研究包括男性和女性创伤患者。我们认为这些临床研究将很重要 由于它们将允许我们比较T/HS模型中观察到的结果与创伤中观察到的结果 患者。