GASTRIC MUCOSAL PERMEABILITY AND CYTOPROTECTION

胃粘膜通透性和细胞保护

• 批准号: 3227685
• 负责人: LAURENCE Y CHEUNG
• 金额: $ 10.17万
• 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 1991-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3227685
• 关键词: acid base balance; aminopyrimidine; aspirin; atropine; bicarbonates; cellular pathology; cyclic GMP; electrical potential; gastric acid; gastric juice inhibitor; gastric mucosa; gastrins; gastrointestinal agents; gastrointestinal circulation; gastrointestinal circulatory insufficiency; gastrointestinal epithelium; gastrointestinal pharmacology; ion transport; mathematical model; membrane permeability; microelectrodes; peptic ulcer; prostaglandin E; radioimmunoassay; radiotracer

Recently, gastric mucosa has been shown to actively secrete bicarbonate (HCO3-) into the lumen. This observation leads to a hypothesis that active secretion of HCO3- may be another important cytoprotective mechanism of the gastric mucosa, since the secreted HCO3-is likely to neutralize the intraluminal acid at the mucosal surface. To assess this hypothesis, the proposed studies are designed (1) to evaluate the role of HCO3- secretion on the acid-base status of the mucosa by measuring intramural pH and (2) to examine the changes in the rate of HCO3- secretion following various stimuli. They include (1) acetylsalicylic acid, a known gastric irritant, (2) Prostaglandin E2, a cytoprotective agent against experimental ulcerations, and (3) ischemia, a predisposing factor in acute ulcerogenesis. In addition, the following studies will determine if HCO3- secretion is affected by secretagogues such as acetylcholine, histamine and pentagastrin and/or mediated by cGMP. The experimental model for these studies will be an in vivo canine stomach which permits the calculation of HCO3- secretion by measuring intragastric pCO2 and pH as described by Garner and Flemstrom. This technique will be added to our present ability to measure gastric blood flow by gamma-labeled microspheres, mucosal cGMP by radioimmunoassay and intramural pH by the microelectrode technique.

最近，胃粘膜已被证明能够积极分泌碳酸氢盐（HCO3-） 进入管腔。 这一观察结果得出一个假设，即主动分泌 HCO3-可能是胃粘膜另一个重要的细胞保护机制， 因为分泌的 HCO3- 可能会中和管腔内的酸 粘膜表面。 为了评估这一假设，拟议的研究设计 (1)评价HCO3-分泌对体内酸碱状态的作用 通过测量粘膜内pH值和(2)来检查粘膜速率的变化 各种刺激后 HCO3- 分泌。 它们包括 (1) 乙酰水杨酸 酸，一种已知的胃刺激物，(2) 前列腺素 E2，一种细胞保护剂 对抗实验性溃疡，以及（3）缺血，这是一种诱发因素 急性溃疡发生。 此外，以下研究将确定 HCO3- 分泌受乙酰胆碱、组胺等促分泌剂的影响 五肽胃泌素和/或由 cGMP 介导。 这些研究的实验模型 将是一个体内犬胃，可以计算 HCO3- 通过测量胃内 pCO2 和 pH 值来分泌，如 Garner 和 弗莱姆斯特罗姆。 这项技术将被添加到我们目前的测量能力中 胃血流通过γ标记微球，粘膜cGMP通过 采用微电极技术进行放射免疫测定和壁内 pH 值测定。