NUTRIENT INDUCED GASTRIC PROTECTION--ROLE OF CCK

营养诱导的胃保护——CCK 的作用

• 批准号: 2458911
• 负责人: DAVID W MERCER
• 金额: $ 9.92万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2458911
• 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; 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.

缩胆囊素(CCK)是一种由CCK细胞分泌的肠肽。 十二指肠和空肠近端。饮食对肠道的主要刺激作用 释放它的是完整的蛋白质和脂肪酸。最近的观察结果 暗示这种肠肽可能有一个更基本的目的 而不是简单地协调一顿饭的消化。事实证明，CCK 能够维持胃粘膜的完整性 破坏性的流明侮辱。因此，营养素似乎很可能 摄入的食物中含有的物质会刺激肠肽的释放， 例如CCK，它不仅协调消化过程，而且还 促进肠道健康，使肠道更能抵抗 经常伴随用餐的管状刺激物。胃损伤的原因 过量饮酒或摄入阿司匹林仍然是一种 上消化道出血的主要原因。此外，胃部 溃疡仍然是一个主要的临床问题。因此，总体假设 这项研究的建议是，饮食肠道营养素诱导 释放内源性CCK并通过这种释放，使胃 上皮细胞对潜在损伤的抵抗力增强 否则就会出现的重大挑战。的精确条件 哪些CCK介导其保护作用及其机制(S) 对这些行为的责任仍有待充分阐明。这是一种 在这种情况下，本研究提案将涉及以下五个方面 明确的目标。第一个目标将是描述以下条件的特征 哪种外源性CCK可防止胃损伤。第二个目标将是 确定营养诱导的内源性CCK释放是否改变了 胃上皮细胞维持其完整性的能力 一种破坏性的侮辱。第三个目标将确定胃的作用 粘膜血流量在营养诱导的胃保护中发挥作用。这个 第四个目的是阐明外源性CCK对胃的影响 上皮离子转运作为一种潜在的保护机制。五号 目的研究营养素对胃Na+，K+-ATPase的影响 活动。这项研究提案的结果将澄清 营养素在胃粘膜固有防御系统中的重要性 并加深我们对人脑的生理功能的认识 内源性肠肽，CCK。