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.

糖尿病患者胃肠道动力失调是发病的重要原因。分子和细胞基础，更不用说这种疾病的有效治疗管理，尚未确定。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，该计划项目是广泛的，跨学科的，跨学科的和多部门的，但高度集中在肠道系统。科学目标通过三个高度综合的项目实现，包括8个具体目标和两个核心。本申请中的研究人员不仅来自胃肠病学和生理学，而且来自神经学、免疫学、放射学、外科和定量成像科学。项目I（糖尿病胃肠病的病理生物学）将研究nNOS和HO/CO通路在调节ICC生物学中的作用。这些途径的失调导致糖尿病胃肠病。项目2（自身免疫和糖尿病运动障碍）重点关注神经元自身免疫作为糖尿病肠道神经病变和运动障碍的原因的作用。项目3（糖尿病肠病中的神经体液调节）将评价一种新的整合神经体液轴，包括肠促胰岛素、GLP-1、氮能神经传递障碍和人类糖尿病神经病变中的交感神经功能障碍。行政核心A将领导和整合所有计划项目活动。成像核心B将为项目之间存储和共享图像数据提供集中资源，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，这个高度互动的计划将取得重大进展，了解糖尿病肠道系统的病理生物学，并将这些知识转化为新的诊断工具和治疗。