ROLE OF GASTRIC BLOOD FLOW IN ACUTE ULCEROGENESIS

胃血流在急性溃疡发生中的作用

• 批准号: 3233477
• 负责人: LAURENCE Y CHEUNG
• 金额: $ 19.85万
• 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 1994-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3233477
• 关键词: adenosine; aspirin; disease /disorder model; dogs; ethanol; flame photometry; gastric mucosa; gastritis; gastrointestinal circulation; gastrointestinal disorder diagnosis; gastrointestinal hemorrhage; granulocyte; histamine; hydrogen; ischemia; isoproterenol; leukotrienes; platelet activating factor; potentiometry; prostaglandins; radiotracer; ulcer; vascular endothelium permeability; vascular resistance; vasodilators

Superficial erosive gastritis may account for as much as 40% of upper gastrointestinal bleeding episodes. In most instances, bleeding from thee acute gastric erosions is related to the excessive use of salicylate- containing compounds or alcohol. Exposure of the gastric mucosa to luminal aspirin or alcohol results in a significant increase in gastric mucosal blood flow (GMBF) as measured to the entire stomach or a large segment of the stomach. The increase in GMBF is interpreted as a compensatory response of the stomach to acid or chemical injury. However, when GMBF to the site of erosion formation is measured, focal mucosal ischemia has been demonstrated. To further define the role of GMBF in acute gastric mucosal ulcerogenesis, the proposed studies are designed to 1) determine the mediator or the vasodilator responsible for this overall increase in GMBFk, 2) characterize the microcirculatory changes that result in focal ischemia and, 3) examine factors that may protect against focal ischemia. These studies will utilize an ex vivo mechanically-perfused segment of the dog's stomach. The first goal will be pursued by determining the time course of changes in gastric vascular resistance following mucosal exposure to ethanol and salicylates. These studies will use competitive antagonists and synthesis inhibitors to assess the role of endogenous histamine, adenosine, and prostaglandins as mediators of the overall increase in GMBF during injury. The second aim will be achieved by identifying microvascular events associated with the development of focal mucosal ischemia. In this regard these experiments will determine the relative significance of effects of leukotrienes, proulcerogenic actions of platelet activating factor, involvement of granulocytes in capillary obstruction, and changes in vascular permeability resulting in edema development. The last objective will be accomplished by assessing the protective effect of factors which reduce the severity of focal mucosal ischemia. Several vasodilators such as adenosine analogues, prostaglandins, and isoproterenol will be tested for the degree of protection against focal ischemia and salicylate or ethanol-induced ulcers. These proposed studies will provide new insight into the patho-physiology of acute gastric ulcers. Clinical application of such knowledge may be beneficial in the prevention and treatment of superficial erosive diseases of the gastric mucosa.

浅表性糜烂性胃炎可能占上消化道疾病的40% 胃肠道出血发作。在大多数情况下，从你身上流血 急性胃溃疡与过量使用水杨酸盐有关- 含有化合物或酒精的。胃粘膜对鲁米诺的暴露 阿司匹林或酒精导致胃粘膜显著增加 血流量(GMBF)，测量到整个胃或很大一部分 胃部。GMBF的增加被解释为一种补偿 胃对酸或化学损伤的反应。然而，当GMBF到 测量糜烂形成的部位，局灶性粘膜缺血 演示了。进一步明确GMBF在急性胃粘膜中的作用 关于溃疡的发生，拟议的研究旨在1)确定 导致GMBFk总体增加的介质或血管扩张剂， 2)描述导致局灶性缺血的微循环变化 以及，3)检查可能对局灶性缺血具有保护作用的因素。这些 研究将利用狗的体外机械灌流节段 胃。 第一个目标将通过确定变化的时间进程来实现 胃粘膜无水乙醇暴露后胃血管阻力 水杨酸盐。这些研究将使用竞争性拮抗剂和合成 用于评估内源性组胺、腺苷和 前列腺素作为损伤期间GMBF总体增加的中介。 第二个目标将通过识别微血管事件来实现 与局灶性粘膜缺血的发生发展有关。在这方面， 这些实验将确定以下效应的相对重要性 白三烯，血小板激活因子的促溃疡作用， 粒细胞在毛细血管阻塞中的参与，以及 血管通透性导致水肿发展。 最后一个目标将通过评估保护效果来实现 降低局灶性粘膜缺血严重程度的因素。几个 血管扩张剂，如腺苷类似物、前列腺素和异丙肾上腺素 将测试对局灶性缺血的保护程度和 水杨酸盐或乙醇引起的溃疡。 这些拟议的研究将为病理生理学提供新的见解。 急性胃溃疡。这种知识的临床应用可能是 有益于浅表腐蚀性疾病的防治 胃粘膜的组织。