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 通过生产几种微循环调节微循环 血管活性物质，包括一氧化氮等血管扩张剂 前列环蛋白和诸如内皮素-1之类的收缩者。生产改变 在这些内皮衍生的因素中，已被认为是一种启动 微循环功能障碍中的事件，可能代表基础 各种临床环境中多个器官损伤的原因。这 拟议的研究的目标是检查 这些内皮衍生的因子在胃微循环中 各种条件。要研究的条件包括：1） 生理条件，2）补体C5A和FMLP的给药 （甲基 - 核基 - 甲基 - 苯丙氨酸）激活循环的 白细胞，已知在败血症期间发生的疾病，3） 缺血/再灌注，是低血压和冲击的结果，这是 由于自由基产生而导致内皮细胞损伤。这些 研究将利用一个机械化的段 狗的肚子。前列环蛋白的组织和血液水平的变化以及 内皮素-1将通过酶免疫测定和一氧化氮测量 通过上述实验条件下的微电极技术。 胃微血管损伤也将通过血管变化评估 血浆蛋白，血管抗性，白细胞的渗透性 依从性和自由基生成。 我们假设有这些合成的反馈调节 在正常条件下，内皮衍生的因素。 这些反馈 机制通过减弱变化来保护胃微循环 在血管渗透性和血管抗性中 血管活性剂。但是，这种正常的反馈机制可能是 白细胞或自由基依赖性内皮后的受损 受伤，如脓毒症和休克等临床环境中发生的那样。 该应用程序的拟议研究将提供新信息 关于内皮衍生因素在发展中的作用 胃微血管损伤，这是胃粘膜的起始事件 受伤。由于胃是受到不利影响的器官 休克，败血症和多器官衰竭的患者，更好 了解胃微循环变化应该是有益的 据我们了解其他器官功能障碍。