DEVELOPMENTALLY IMPAIRED MOTOR ACTIVITY IN THE CYSTIC FIBROSIS SMALL INTESTINE

囊性纤维化小肠运动活动发育受损

• 批准号: 7959580
• 负责人: ROBERT C DE LISLE
• 金额: $ 5.87万
• 依托单位: UNIVERSITY OF KANSAS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7959580
• 关键词: Age; Behavior; Cells; Cessation of life; Childhood; Computer Retrieval of Information on Scientific Projects Database; Cystic Fibrosis; Development; Enzymes; Exhibits; Experimental Models; Failure; Failure to Thrive; Functional disorder; Funding; Gastrointestinal Motility; Goals; Grant; Growth; Health; Hereditary Disease; Human; Inflammatory disease of the intestine; Institution; Intestinal Motility; Intestines; Life; Measures; Metabolic; Metabolism; Molecular; Motor Activity; Muscle; Nutritional; Outcome; Prostaglandins; Regulation; Research; Research Personnel; Resources; Small Intestines; Source; Time; United States National Institutes of Health; cystic fibrosis mouse; cystic fibrosis patients; design; improved; motility disorder; novel therapeutics; nutrition; postnatal

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Background: Small intestinal motility protects against bacterial overgrowth and is important for proper nutrition. Cystic fibrosis (CF) is one of the most common lethal genetic diseases and about half of CF patients have dysfunction of gastrointestinal motility and small intestinal bacterial overgrowth. Childhood failure-to-thrive and life-long nutritional problems are common in CF. Rationale: Poor nutrition is strongly correlated with the progression to airway failure and death in CF. At what age intestinal dysmotility develops in CF, and by what mechanisms, are not known. The long term goal is to understand intestinal dysfunction in CF in order to provide new therapeutic directions to improve health. Questions: The goal is to determine the relationships between bacterial overgrowth, inflammation, and intestinal muscle dysfunction during postnatal development. Design: The CF mouse model exhibits similar intestinal problems as human CF patients and will be used as an experimental model for this project. The objectives in this application are to determine the temporal relationships between altered metabolism of prostaglandins, intestinal muscle dysfunction, and bacterial overgrowth during development of the CF mouse small intestine. Outcomes: (1) Determine when prostaglandin metabolism is altered, by measuring expression of prostaglandin metabolic enzymes and levels of prostaglandins; (2) Determine when circular muscle activity is impaired, by measuring muscle behavior; and (3) Determine when abnormal bacterial growth occurs. The developmental time courses of these changes will be revealing about the causes of intestinal dysfunction in CF.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 背景：小肠运动可防止细菌过度生长，对适当的营养很重要。囊性纤维化是最常见的致死性遗传病之一，约有一半的囊性纤维化患者存在胃肠动力障碍和小肠细菌过度生长。儿童期发育不良和终生营养问题在慢性萎缩性胃炎中很常见。理论基础：营养不良与慢性阻塞性肺疾病发展为呼吸道衰竭和死亡密切相关。目前尚不清楚什么年龄段的患者会出现肠动力障碍，其发病机制也不清楚。长期目标是了解CF的肠道功能障碍，以便为改善健康提供新的治疗方向。问题：目标是确定细菌过度生长、炎症和出生后发育过程中肠道肌肉功能障碍之间的关系。设计：CF小鼠模型表现出与人类CF患者相似的肠道问题，并将作为本项目的实验模型。本应用的目的是确定在CF小鼠小肠发育过程中前列腺素代谢改变、肠道肌肉功能障碍和细菌过度生长之间的时间关系。结果：(1)通过测量前列腺素代谢酶的表达和前列腺素水平来确定前列腺素代谢何时改变；(2)通过测量肌肉行为来确定环行肌活动何时受损；以及(3)确定何时发生异常细菌生长。这些变化的发展时间进程将揭示CF肠功能障碍的原因。