NUTRIENT INDUCED GASTRIC PROTECTION--ROLE OF CCK

胆囊收缩素（CCK）是一种肠肽，由位于胃肠道的CCK细胞产生。 十二指肠和近端空肠。主要的饮食肠道刺激 是完整的蛋白质和脂肪酸。最近的观察 这表明这种肠肽可能具有更基本用途 而不仅仅是协调消化一顿饭。研究表明，CCK 能够维持胃粘膜的完整性， 破坏性管腔损伤。因此，似乎营养素 所含的蛋白质刺激肠道肽的释放， 例如CCK，它不仅协调消化过程，而且 促进肠道健康，使肠道更能抵抗来自 经常伴随进餐的管腔刺激物。胃损伤， 过量饮酒或摄入阿司匹林仍然是一个 上消化道出血的主要原因。此外，胃 溃疡仍然是主要的临床问题。因此，总体假设 这项研究建议的一个重要方面是，饮食中的肠道营养素会引起 内源性CCK的释放，并通过这种释放，使胃 上皮变得更能抵抗来自潜在损害的损伤 否则会发生管腔挑战。精确的条件， CCK介导其保护作用以及机制 对这些行动负责的人仍有待充分查明。这就是 在这种情况下，本研究建议将解决以下五个问题 明确的目标。 第一个目标将是描述 外源性CCK可预防胃损伤。第二个目标是 确定营养素诱导的内源性CCK释放是否改变了 胃上皮维持其完整性的能力 伤害性的侮辱第三个目的是确定胃的作用， 粘膜血流在营养诱导的胃保护中起作用。 的 第四个目的是阐明外源性CCK对胃粘膜的影响， 上皮细胞离子转运作为一种潜在的保护机制。第五 目的探讨营养素对胃Na+，K+ ATP酶的影响 活动这项研究计划的结果将澄清 营养素在胃粘膜固有防御系统中的重要性 并增强我们对心脏的生理功能的理解， 内源性肠肽

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.