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: 8167987
• 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: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167987
• 关键词: Age; Behavior; 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; Motor Activity; Muscle; Nutritional; Outcome; Prostaglandins; 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的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 背景：小肠运动可以防止细菌过度生长，对适当的营养很重要。囊性纤维化（CF）是最常见的致死性遗传病之一，约一半的CF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身营养问题在CF中很常见。原理：营养不良与CF中气道衰竭和死亡的进展密切相关。CF在什么年龄发生肠动力障碍，以及通过何种机制发生尚不清楚。长期目标是了解CF中的肠道功能障碍，以提供新的治疗方向来改善健康。问题：我们的目标是确定细菌过度生长，炎症和肠道肌肉功能障碍之间的关系，在出生后的发展。设计：CF小鼠模型表现出与人类CF患者相似的肠道问题，并将用作本项目的实验模型。本申请的目的是确定CF小鼠小肠发育过程中异甘草素代谢改变、肠肌肉功能障碍和细菌过度生长之间的时间关系。成果：（1）通过测量前列腺素代谢酶的表达和前列腺素的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形肌活动何时受损;和（3）确定异常细菌生长何时发生。这些变化的发展时间过程将揭示CF肠道功能障碍的原因。