The Role of Intestinal Inflammation in the Pathophysiology of IBS

描述（由申请人提供）： 这个职业发展应用程序有两个组成部分：一。一个指导研究项目，和二。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与某些患者的IBS病因有关。最近的动物模型研究表明，这些因素可能参与了肠道动力障碍和内脏高敏感性的病理生理机制。然而，肠道炎症和粘膜免疫激活的作用还没有充分和系统地研究IBS患者。本研究拟比较腹泻型肠易激综合征（D-IBS）患者和对照组的亚临床黏膜炎症。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，阶段性运动和平滑肌张力。我们将研究33例患有D-IBS的IBS患者和33名健康对照。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。本提案的教育/培训部分是根据Ringel博士导师的建议制定的：Balfour Sartor博士是世界知名的肠道炎症专家和研究人员，William Whitehead博士是世界知名的功能性GI疾病专家和研究人员。我们建议正式的课程以及实验室培训，旨在扩大和增加林格尔博士在这些领域的理论和研究方法的知识和技能。总体目标是将Ringel博士确立为独立资助的翻译研究人员。因此，将在授予期间开发的方法，结果和协议将用于设计机制干预研究，并作为提交未来（NIH）赠款的初步数据。

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.