ENDOTHELIAL INJURY IN POSTNATAL INTESTINE

产后肠道内皮损伤

• 批准号: 2204716
• 负责人: PHILIP T. NOWICKI
• 金额: $ 18.46万
• 依托单位: CHILDREN'S HOSPITAL (COLUMBUS)
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-05-01 至 1997-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2204716
• 关键词: colitis; disease /disorder model; hemodynamics; injury; ischemia; mesentery; nitric oxide; perfusion; reperfusion; swine; vascular endothelium; vasodilators

DESCRIPTION: The investigators propose to study the effects of endothelial cell injury on gut hemodynamics in the pathogenesis of necrotizing enterocolitis (NEC). They propose that clinically relevant gut ischemia develops within localized areas of the gut and occurs secondary to antecedent damage to the vascular endothelium which lines the intestinal circulation. Specifically, they submit that endothelial cell damage is an essential part of the early pathogenesis of NEC; this injury attenuates production of endothelium-derived relaxing factor (EDRF), impairs regional perfusion and eventually compromises parenchymal viability. To test this hypothesis, the proposed experiments are designed: (1) to determine if endothelial cell injury attenuates EDRF production by postnatal mesenteric arteries in an age- dependent fashion; (2) to examine if endothelial cell injury alters the pressure-flow relationship within postnatal mesenteric arteries in an age- dependent fashion; (3) to determine if structural injury to endothelial cells occurs in an age-dependent fashion; and (4) to examine if endothelial cell injury alters the response of the intestinal circulation to exogenous constrictor and dilator stimuli in an age- dependent fashion. Endothelial cell injury will be induced by application of ischemia/reperfusion, insofar as this method is reproducible, inexpensive and clinically relevant. Studies will be conducted in 1-, 3- and 35-day old swine, a species which has proven to be an excellent model for the study of developmental physiology. Assessment of the effects of endothelial cell injury on EDRF production will include in vitro techniques, wherein relaxation of precontracted artery rings and production of cGMP are used as markers of EDRF production. Other studies will explore the effects of endothelial cell injury on gut hemodynamics in vivo. The investigators expect that results of this work may implicate endothelial damage in causing significant, age-dependent effects on gut vascular function. If so, they propose that such injury may be common to a number of different "trigger events" leading to NEC.

描述：研究人员建议研究 内皮细胞损伤对肠道血流动力学的影响 坏死性小肠结肠炎（NEC）。 他们提出临床相关的 肠道局部缺血在肠道的局部区域内发展 继发于血管内皮的先前损伤， 肠道循环。 具体来说，他们认为内皮细胞 细胞损伤是NEC早期发病机制的重要组成部分， 损伤减弱内皮源性舒张因子的产生 （EDRF），损害局部灌注，并最终损害 实质活力 为了验证这一假设， 实验设计：（1）确定内皮细胞损伤是否 减弱出生后肠系膜动脉的EDRF产生， 依赖性方式;（2）检查内皮细胞损伤是否改变了 新生儿肠系膜动脉压力-血流关系的研究 年龄依赖性方式;（3）确定是否结构性损伤， 内皮细胞以年龄依赖的方式发生;和（4）检查 如果内皮细胞损伤改变了肠道的反应 循环对外源性收缩和扩张刺激的反应 依赖的方式。 内皮细胞损伤将由 缺血/再灌注的应用，只要这种方法是 可重复的、廉价的和临床相关的。 研究将 在1日龄、3日龄和35日龄猪中进行，该种属已被证明 是研究发育生理学的极好模型。 评估内皮细胞损伤对EDRF产生的影响 将包括体外技术，其中预收缩的 动脉环和cGMP的产生被用作EDRF的标志物 生产 其他研究将探索内皮细胞的作用， 对在体肠道血流动力学的损伤。 调查人员预计， 这项工作的结果可能涉及内皮损伤， 对肠道血管功能有显著的年龄依赖性影响。 如果是这样，他们 我认为，这种伤害可能是常见的一些不同的“触发 事件”导致NEC。