Pathobiology of the Enteric System

糖尿病、饮食失调和特发性疾病患者的胃排空障碍是发病率的重要原因。目前有效管理胃排空障碍的方法是无效的。本项目的目的是促进我们对胃组织营养不良变化和反馈机制的理解，这些变化是胃排空紊乱和胃运动障碍的原因，并制定策略来预防或逆转这些变化并恢复胃排空，这些策略可在人体临床试验中进行测试。科学目标通过三个高度整合的项目和三个核心来实现。项目1（糖尿病性胃肠病病理生物学）研究HO1在预防糖尿病性胃轻瘫发展中的作用以及糖尿病中HO1活性的调节机制。项目2 （Mechanisms of Gastric Dysfunction in Chronic Caloric Restriction）研究了胃肌细胞营养不良在慢性或慢性间歇性热量缺乏相关的运动障碍中的作用，以及营养不良的改变是否通过减少IGF-1和HO-1的产生介导。项目3（糖尿病性肠病的神经体液调节）通过临床试验评估HO1表达增加对糖尿病患者胃排空的影响，评估血糖控制对糖尿病患者胃排空的影响，确定十二指肠-胃反馈受损导致胃底松弛受损和胃排空快速的机制。行政核心A将领导所有计划项目活动。Imaging Core B将提供先进的软件，用于体内和体外成像的严格定量分析，以及患者胃的动态MR成像。生理表征和数据管理核心C将开发和管理电子动物研究记录，使所有项目研究人员可以在单一电子记录中获得所有研究数据。这个高度整合的项目将在理解胃排空障碍中肠道系统的病理生物学方面取得重大进展，并将这些知识转化为新的诊断工具和治疗方法。

Disorders of gastric emptying in patients with diabetes, eating disorders and in idiopathic conditions are a significant cause of morbidity. Current approaches for effectively managing gastric emptying disorders are ineffective. The objective of this Program Project is to advance our understanding of the dystrophic changes in the gastric musculature and feed back mechanisms that are the cause of disorders of gastric emptying and gastric motor disturbances and develop strategies to prevent or reverse these changes and restore gastric emptying that are testable in human clinical trials. The scientific objectives are met through three highly Integrated projects and three cores. Project 1 (Pathobiology of Diabetic Gastroenteropathy) studies the role of HO1 in preventing the development of diabetic gastroparesis and the mechanisms that regulate HOI activity in diabetes. Project 2 (Mechanisms of Gastric Dysfunction in Chronic Caloric Restriction) studies the role of cellular dystrophy in the gastric musculature in dysmotilities associated with chronic or chronic intermittent caloric deficit and whether the dystrophic changes are mediated by reduced production of IGF-1 and HO-1. Project 3 (Neurohumoral Regulation in Diabetic Enteropathy) evaluates in clinical trials the effect of increasing HO1 expression on gastric emptying in patients with diabetes, assesses the Impact of glycemic control on gastric emptying in diabetic patients and determines the mechanism accounting for Impaired duodenal-gastric feedback responsible for impaired fundic relaxation and rapid gastric emptying. The Administrative Core A will provide leadership of all Program Project activities. The Imaging Core B will provide advanced software for rigorous quantitative analysis for in vivo and in vitro imaging, and dynamic MR imaging on the stomach in patients. The Physiological Characterization and Data Management Core C will develop and manage an Electronic Animal Research Record that makes available In a single electronic record all research data to all Program investigators. This highly-integrated Program will make significant progress toward understanding the pathobiology of the enteric system in gastric emptying disorders and translate this knowledge into new diagnostic tools and therapy.