NUTRIENT INDUCED GASTRIC PROTECTION--ROLE OF CCK

营养诱导的胃保护——CCK 的作用

• 批准号: 2838151
• 负责人: DAVID W MERCER
• 金额: $ 6.83万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 1999-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2838151
• 关键词: adenosinetriphosphatase; alcoholic beverage consumption; aspirin; chemoprevention; chlorine; cholanate compound; cholecystokinin; electrophysiology; enzyme activity; gastric mucosa; gastrointestinal epithelium; gastrointestinal pharmacology; gastrointestinal stimulator; hormone receptor; hormone regulation /control mechanism; ion transport; laboratory rabbit; laboratory rat; medical rehabilitation related tag; nutrient intake activity; nutrition related tag; radioactive microsphere technique; radioimmunoassay; sodium potassium exchanging ATPase; somatostatin

Cholecystokinin (CCK) is a gut peptide produced by CCK cells located in the duodenum and proximal jejunum. The major dietary intestinal stimuli for its release are intact proteins and fatty acids. Recent observations suggest that this gut peptide may serve a far more fundamental purpose than simply coordinating digestion of a meal. It has been shown that CCK is capable of maintaining gastric mucosal Integrity In the face of a damaging luminal insult. Consequently, it seems likely that nutrients contained within an Ingested meal stimulate the release of gut peptides, such as CCK, that not only coordinate the digestive process, but also promote intestinal health and render the gut more resistant to damage from luminal irritants that often accompany a meal. Gastric injury from excessive alcohol consumption or ingestion of aspirin continues to be a major cause of upper gastrointestinal bleeding. Further, gastric ulceration remains a major clinical problem. Thus, the overall HYPOTHESIS of this research proposal is that dietary intestinal nutrients elicit the release of endogenous CCK and through such release, enables the gastric epithelium to become more resistant to injury from potentially damaging luminal challenges that would otherwise occur. The precise conditions by which CCK mediates its protective effects as well as the mechanism(s) responsible for these actions remain to be fully elucidated. This being the case, the present research proposal will address the following five specific aims. The first aim will be to characterize the conditions under which exogenous CCK prevents gastric injury. The second aim will be to determine whether nutrient induced release of endogenous CCK alters the ability of the gastric epithelium to maintain its integrity in response to a damaging insult. The third aim will ascertain the role that gastric mucosal blood flow plays in nutrient induced gastric protection. The fourth aim will elucidate the effects of exogenous CCK on gastric epithelial ion transport as a potential protective mechanism. The fifth aim will examine the effects of nutrients on gastric Na+, K+ ATPase activity. The results of this research proposal will clarify the importance of nutrients in the intrinsic gastric mucosal defense system and enhance our understanding of the physiological function of the endogenous gut peptide, CCK.

胆囊收缩素 (CCK) 是一种由 CCK 细胞产生的肠道肽，位于 十二指肠和近端空肠。主要饮食刺激肠道 其释放的是完整的蛋白质和脂肪酸。最近的观察 表明这种肠道肽可能有更根本的用途 而不仅仅是协调膳食的消化。事实证明，CCK 能够维持胃粘膜的完整性 破坏性的管腔损伤。因此，营养素似乎很可能 摄入的膳食中所含的物质会刺激肠道肽的释放， 例如 CCK，它不仅协调消化过程，还 促进肠道健康，使肠道更能抵抗来自肠道的损害 进餐时经常出现的管腔刺激物。胃损伤来自 过量饮酒或服用阿司匹林仍然是一个问题 是上消化道出血的主要原因。另外，胃 溃疡仍然是一个主要的临床问题。因此，总体假设 这项研究建议的重点是膳食肠道营养素会引起 内源性 CCK 的释放，并通过这种释放，使胃 上皮细胞对潜在破坏性损伤的抵抗力更强 否则会发生的管腔挑战。精确条件由 CCK 介导其保护作用以及机制 对这些行动的责任仍有待充分阐明。这个存在 在这种情况下，本研究计划将解决以下五个问题 具体目标。 第一个目标是描述条件下的特征 外源性 CCK 可预防胃损伤。第二个目标是 确定营养诱导的内源 CCK 释放是否改变 胃上皮保持其完整性的能力 一种破坏性的侮辱。第三个目标是确定胃的作用 粘膜血流在营养诱导的胃保护中发挥作用。 这 第四个目标是阐明外源性 CCK 对胃的影响 上皮离子转运作为潜在的保护机制。第五 目的将检查营养物质对胃Na+、K+ ATP酶的影响 活动。该研究计划的结果将阐明 营养物质在胃粘膜内在防御系统中的重要性 并加深我们对生理功能的了解 内源性肠肽，CCK。