ENDOTHELIAL FACTORS ON GASTRIC MICROCIRCULATION

胃微循环的内皮因素

• 批准号: 2139522
• 负责人: LAURENCE Y CHEUNG
• 金额: $ 22.14万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-12-01 至 1999-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2139522
• 关键词: acute disease /disorder; adenosine; angiotensin II; cell adhesion; chemoattractants; complement; dogs; endothelin; enzyme linked immunosorbent assay; free radicals; gastrointestinal circulation; histamine; ischemia; leukocyte activation /transformation; microelectrodes; nitric oxide; norepinephrine; peptic ulcer; prostacyclins; vascular endothelium; vascular endothelium permeability; vascular resistance

Recent studies have shown that endothelial cells play an active role in the regulation of the microcirculation through production of several vasoactive substances, including vasodilators such as nitric oxide and prostacyclin, and constrictors such as endothelin-1. Altered production of these endothelial-derived factors has been postulated as an initiating event in microcirculatory dysfunction, and may represent an underlying cause of multiple organ injury in a variety of clinical settings. The goal of the proposed studies is to examine the formation and actions of these endothelial-derived factors in the gastric microcirculation under various conditions. The conditions to be studied include: 1) physiological conditions, 2) administration of complement C5a and FMLP (formyl-leucyl-methionyl-phenylalanine) which activate circulating leukocytes, a condition known to occur during sepsis, and 3) ischemia/reperfusion, a consequence of hypotension and shock, which causes endothelial cell injury due to free radical generation. These studies will utilize an ex vivo mechanically-perfused segment of the dog's stomach. Changes in tissue and blood levels of prostacyclin and endothelin-1 will be measured by enzyme immunoassays, and nitric oxide by a microelectrode technique under the above experimental conditions. Gastric microvascular injury will also be assessed by changes in vascular permeability to plasma proteins, vascular resistance, leukocyte adherence, and free radical generation. We postulate that there is a feedback regulation of synthesis of these endothelial-derived factors under normal conditions. These feedback mechanisms protect the gastric microcirculation by attenuating changes in vascular permeability and vascular resistance in response to vasoactive agents. However, this normal feedback mechanism may be impaired following leukocyte- or free radical-dependent endothelial injury, as occurs in clinical settings such as sepsis and shock. The proposed studies of this application will provide new information regarding the role of endothelial-derived factors in the development of gastric microvascular injury, an initiating event in gastric mucosal injury. Since the stomach is one of the organs adversely affected in patients with shock, sepsis, and multiple organ failure, a better understanding of gastric microcirculatory changes should be beneficial to our knowledge regarding other organ dysfunctions.

最近的研究表明，内皮细胞在 微循环的调节通过生产几个 血管活性物质，包括血管扩张剂，如一氧化氮和 前列环素和收缩剂如内皮素-1。产量改变 这些内皮源性因子被假定为启动 微循环功能障碍事件，可能代表潜在的 在各种临床环境中引起多器官损伤。的 拟议研究的目标是审查的形成和行动， 这些内皮源性因子在胃微循环下， 各种条件。研究的条件包括：1） 生理条件，2）施用补体C5 a和FMLP （甲酰基-亮氨酰基-甲硫氨酰基-苯丙氨酸），其激活循环 白细胞，这是一种已知在败血症期间发生的疾病，以及3） 缺血/再灌注是低血压和休克的结果， 由于自由基的产生导致内皮细胞损伤。这些 研究将利用离体机械灌注的节段， 狗的肚子组织和血液中前列环素水平的变化， 内皮素-1将通过酶免疫测定法测量， 在上述实验条件下，用微电极技术测定。 胃微血管损伤也将通过血管内皮细胞的变化来评估。 血浆蛋白通透性，血管阻力，白细胞 粘附和自由基生成。 我们假设，有一个反馈调节合成这些 正常情况下的内皮衍生因子。 这些反馈 保护胃微循环的机制是通过减弱 血管通透性和血管阻力 血管活性剂然而，这种正常的反馈机制可能是 白细胞或自由基依赖性内皮细胞 损伤，如在临床环境中发生的，如败血症和休克。 本申请的拟议研究将提供新的信息 关于内皮衍生因子在发展中的作用， 胃微血管损伤是胃粘膜损伤的起始事件 损伤由于胃是一个器官的不利影响， 休克、脓毒症和多器官功能衰竭患者， 了解胃微循环的变化， 我们对其他器官功能障碍的了解。