Pathobiology of the Enteric System

肠道系统病理学

• 批准号: 6949600
• 负责人: JOSEPH H. SZURSZEWSKI
• 金额: $ 125.42万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6949600
• 关键词: clinical research; diabetes mellitus; enteric nervous system; gastrointestinal disorder; gastrointestinal motility /pressure; pathologic process

Dysregulation of the motility of the gastrointestinal tract in diabetic patients is a significant cause of morbidity. The molecular and cellular bases, much less an effective therapeutic management of this disorder, have yet to be identified. The overarching objective of this Program Project is to promote, facilitate and conduct basic, clinical and translational research on the causes of motility disorders with the ultimate goal to identify novel therapeutic treatments. Accordingly, this Program Project is broad, transdisciplinary and interdisciplinary and multidepartmental, but highly focused on the enteric system. The scientific objectives are met through three highly integrated projects that include 8 specific aims, and two cores. The investigators in this application are drawn not only from gastroenterology and physiology but also from neurology, immunology, radiology, surgery and quantitative imaging sciences. Project I (Pathobiology of Diabetic Gastroenteropathy) will study the role of the nNOS and HO/CO pathways in regulating ICC biology. Dysregulation of these pathways results in diabetic gastroenteropathy. Project 2 (Autoimmune and Diabetic Dysmotility) focuses on the role of neuronal autoimmunity as a cause of enteric neuropathy and dysmotility in diabetes. Project 3 (Neurohumoral Regulation in Diabetic Enteropathy) will evaluate a novel integrated neurohumoral axis comprising the incretin, GLP-1, disordered nitrergic neurotransmission and sympathetic dysfunction in diabetic neuropathy in humans. The Administrative Core A will provide leadership and integration of all Program Project activities. The Imaging Core B will provide a centralized resource for storing and sharing image data between projects, will provide advanced software for rigorous quantitative analysis, and will develop new methods for dynamic 3D imaging and image fusion. Through these projects and cores, this highly-interactive program will make significant progress toward understanding the pathobiology of the enteric system in diabetes and translate this knowledge into new diagnostic tools and therapy.

糖尿病患者胃肠道运动失调是发病的重要原因。这种疾病的分子和细胞基础尚未确定，更不用说有效的治疗方法了。该计划项目的总体目标是促进、促进和开展关于运动障碍原因的基础、临床和转化研究，最终目标是确定新的治疗方法。因此，该计划项目范围广泛、跨学科、跨学科和多部门，但高度关注肠道系统。科学目标通过三个高度综合的项目来实现，其中包括 8 个具体目标和两个核心。该申请的研究人员不仅来自胃肠病学和生理学，还来自神经病学、免疫学、放射学、外科和定量成像科学。项目 I（糖尿病胃肠病病理学）将研究 nNOS 和 H2O/CO 通路在调节 ICC 生物学中的作用。这些途径的失调会导致糖尿病胃肠病。项目 2（自身免疫和糖尿病运动障碍）重点研究神经元自身免疫在糖尿病肠神经病变和运动障碍中的作用。项目 3（糖尿病性肠病的神经体液调节）将评估一种新型的综合神经体液轴，包括人类糖尿病神经病中的肠促胰岛素、GLP-1、紊乱的氮能神经传递和交感神经功能障碍。行政核心 A 将领导和整合所有计划项目活动。 Imaging Core B 将提供用于在项目之间存储和共享图像数据的集中资源，将为严格的定量分析提供先进的软件，并将开发动态 3D 成像和图像融合的新方法。通过这些项目 和核心，这个高度互动的项目将在了解糖尿病肠道系统的病理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疗法。