ROLE OF GI PHOSPHOLIPIDS IN ULCER PROTECTION

胃肠道磷脂在溃疡保护中的作用

• 批准号: 3231629
• 负责人: LENARD M LICHTENBERGER
• 金额: $ 14.59万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1983
• 资助国家: 美国
• 起止时间: 1983-12-01 至 1990-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3231629
• 关键词: apical membrane; aspirin; autoradiography; disease /disorder model; disease /disorder prevention /control; dogs; drug adverse effect; duodenal ulcer; gastric mucosa; gastrointestinal epithelium; hydropathy; intestinal mucosa; laboratory rat; liposomes; membrane activity; membrane lipids; peptic ulcer; phospholipids; prostaglandins; radiotracer; surfactant; tissue /cell culture

The physico-chemical basis of the barrier properties of the stomach has yet to be defined. We have reported that the luminal surface of the stomach is uniquely hydrophobic or non- wettable which may prevent luminal (aqueous) ulcerogens from coming in intimate contact with the gastric epithelium. Furthermore, we have demonstrated that certain damaging agents (i.e. aspirin) markedly attenuate this property whereas it is restored by "cytoprotective" prostaglandins. In the present application we plan to continue these studies and further pursue employing both in vitro (Ussing Chamber) and in vivo studies the effects of a number of clinically relevant barrier breakers (aspirin, bile acids, lysolecithin, ethanol) alone and together with prostaglandin on the surface hydrophobicity of the gastric mucosa. The importance of the restoration of surface hydrophobicity to the stomach's ability to recover from damage will also be investigated. We also plan to continue our studies investigating the role of mucosal surface-active phospholipids (SAPL) in the generation of a protective hydrophobic layer by performing morphological, (SAPL-specific stains and autoradiography and at the light and electron microscopic level), biochemical, biophysical and cell biological studies. Since preliminary morphological data indicates that the mucous cells may be involved in active phospholipid synthesis and secretion, we will attempt to study these processes directly in a monolayer culture of purified gastric mucous cells. The information obtained in the biochemical studies on the SAPL composition of the gastric mucosa will be used to formulate liposomal mixtures whose anti-ulcer activity will be tested in several animal models of experimentally-induced ulcerogenesis. We also plan to characterize the fluidity of the lipids of the gastric mucosal surface using fluorescent polarization spectrometry to access its role in the barrier properties of the stomach.

屏障特性的物理化学基础 胃尚未定义。 我们报告说 胃的腔表面是独特的疏水或非 - 润湿可能会防止腔（水溶液）溃疡性 与胃上皮紧密接触。 此外，我们已经证明了某些破坏性 代理（即阿司匹林）显着衰减了此财产，而它 由“细胞保护”前列腺素恢复。 现在 我们计划继续这些研究并进一步追求 使用体外（使用室）和体内研究 许多临床相关的障碍断路器的影响 （阿司匹林，胆汁酸，溶酶体，乙醇）单独并与 前列腺素在胃的表面疏水性上 粘膜。 恢复表面的重要性 疏水性从胃中恢复的能力 也将进行调查。 我们还计划继续学习 研究粘膜表面活性磷脂的作用 （SAPL）在生成保护性疏水层中 表现形态学（SAPL特异性污渍和 放射自显影，在光和电子显微镜水平）， 生化，生物物理和细胞生物学研究。 自从 初步的形态数据表明粘液细胞 可能参与活性磷脂合成和分泌， 我们将尝试直接在单层中研究这些过程 纯化的胃粘液细胞的培养。 信息 在关于SAPL组成的生化研究中获得的 胃粘膜将用于制定脂质体混合物 在几种动物模型中将测试其抗粉状活性 实验诱导的溃疡发生。 我们还计划 表征胃粘膜脂质的流动性 使用荧光极化光谱法访问其表面 在胃的屏障特性中的作用。