The Role of Intestinal Inflammation in the Pathophysiology of IBS

肠道炎症在 IBS 病理生理学中的作用

• 批准号: 7480910
• 负责人: YEHUDA RINGEL
• 金额: $ 15.72万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-25 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7480910
• 关键词: Animal Model; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Area; Award; Biological Assay; Biological Markers; Blood specimen; Chronic; Clinical; Colon; Data; Depth; Development; Diarrhea; Dinoprostone; Disease; Eicosanoids; Enzyme-Linked Immunosorbent Assay; Epidemiologic Studies; Equilibrium; Esthesia; Etiology; Feces; Frequencies; Functional disorder; Funding; Future; Genus Cola; Goals; Gold; Grant; Heterogeneity; Hypersensitivity; Immune; Immune response; Immune system; Immunoassay; Immunologics; Inflammation; Inflammatory; Inflammatory Response; Inflammatory disease of the intestine; Interleukin-10; Interleukin-12; Intervention Studies; Intestinal Mucosa; Intestines; Invasive; Investigation; Knowledge; Laboratories; Lactoferrin; Leukocyte L1 Antigen Complex; Measures; Mediator of activation protein; Mentors; Methodology; Methods; Motor; Mucositis; Muscle Tonus; National Institute of Diabetes and Digestive and Kidney Diseases; Neuropeptides; Pain Threshold; Patient Monitoring; Patients; Peripheral; Physiological; Physiology; Polymerase Chain Reaction; Population Study; Principal Investigator; Procedures; Process; Production; Proteins; Protocols documentation; Regulation; Relative (related person); Report (document); Research; Research Methodology; Research Personnel; Research Project Grants; Role; Sensory; Standards of Weights and Measures; Substance P; Symptoms; Techniques; Therapeutic Intervention; Time; Training; Training Activity; United States National Institutes of Health; Visceral; base; career; cell motility; clinically relevant; cytokine; design; immune function; indexing; interleukin-12 subunit p40; mRNA Expression; motility disorder; peripheral blood; programs; research study; response; skills; theories

DESCRIPTION (provided by applicant): This career development application has two components: I. A mentored research project, and II. Educational/training activities. Epidemiological studies have implicated intestinal inflammation and chronic activation of the immune system in the etiology of IBS for some patients. Recent research in animal models suggests that these factors can be involved in the pathophysiological mechanisms responsible for intestinal dysmotility and visceral hypersensitivity. However, the role of intestinal inflammation and mucosal immune activation has not been adequately and systematically investigated in patients with IBS. In the proposed research project we will compare sub-clinical mucosal inflammation between patients with diarrhea predominant IBS (D-IBS) and control. We will specifically look at pro- and anti-inflammatory cytokines and inflammatory-associated neuropeptides. Analyses will be performed by Real-time PCR and ELISA techniques to verify results. In our second aim we will investigate whether alterations in inflammatory markers are associated with alterations with relevant intestinal physiology including colonic pain thresholds, phasic motility, and smooth muscle tone. We will study 33 IBS patients with D-IBS and 33 healthy controls. Intestinal physiological data will be collected on the same study population of an NIH supported study on the heterogeneity of IBS (NIDDK Grant DK 31369, Whitehead PI) on which Dr. Whitehead is collaborating with Dr. Ringel. The educational/training components of this proposal have been developed with the advice of Dr. Ringel's mentors: Dr. Balfour Sartor is a world renowned expert and researcher in intestinal inflammation and Dr. William Whitehead is a world renowned expert and researcher in functional Gl disorders. We propose formal coursework as well as laboratory training aiming to expand and increase Dr. Ringel's knowledge and skills in theories and research methodologies in these areas. The overall goal is to establish Dr. Ringel as an independently-funded translational researcher. Thus, the methodologies, results and protocols that will be developed during the award will be used to design mechanistic intervention studies and as preliminary data for submission of future (NIH) grants.

描述（由申请人提供）： 该职业发展申请有两个组成部分：I. 指导研究项目，II. 指导研究项目。教育/培训活动。流行病学研究表明，肠道炎症和免疫系统的慢性激活是某些患者 IBS 的病因。最近的动物模型研究表明，这些因素可能参与导致肠道运动障碍和内脏过敏的病理生理机制。然而，肠道炎症和粘膜免疫激活的作用尚未在 IBS 患者中得到充分、系统的研究。在拟议的研究项目中，我们将比较腹泻为主的 IBS (D-IBS) 患者和对照患者之间的亚临床粘膜炎症。我们将特别关注促炎和抗炎细胞因子以及炎症相关神经肽。将通过实时 PCR 和 ELISA 技术进行分析以验证结果。在我们的第二个目标中，我们将研究炎症标志物的改变是否与相关肠道生理学的改变相关，包括结肠疼痛阈值、相性运动和平滑肌张力。我们将研究 33 名患有 D-IBS 的 IBS 患者和 33 名健康对照者。将在 NIH 支持的 IBS 异质性研究（NIDDK Grant DK 31369，Whitehead PI）的同一研究人群中收集肠道生理数据，Whitehead 博士与 Ringel 博士合作开展该研究。该提案的教育/培训部分是根据 Ringel 博士导师的建议制定的：Balfour Sartor 博士是肠道炎症领域的世界知名专家和研究员，William Whitehead 博士是功能性胃肠道疾病领域的世界知名专家和研究员。我们提出正式的课程作业以及实验室培训，旨在扩展和提高林格尔博士在这些领域的理论和研究方法方面的知识和技能。总体目标是将林格尔博士打造为一名独立资助的转化研究员。因此，获奖期间将开发的方法、结果和方案将用于设计机械干预研究，并作为提交未来（NIH）拨款的初步数据。