Minority Predoctoral Fellowship Program

描述(申请人提供)：肠易激综合征(IBS)是一种慢性胃肠道疾病，以腹痛和运动障碍为特征。该综合征常与炎症性肠病(IBD)相混淆。IBD和IBS的病因不明，其确切发病机制尚不清楚。紧张的生活事件会加重IBS和IBD的症状。似乎应激可以改变结肠上皮的通透性，并影响关键调节细胞因子的产生。这一建议的中心假设是，先前的肠道炎症增加了结肠上皮对应激诱导的通透性的敏感性，使内毒素能够穿越，与受体结合，导致刺激性神经元的上调。该计划的具体目的是：1)测量既往肠道炎症对应激诱导的上皮运输和膜完整性改变的影响；2)确定既往炎症对应激诱导的细胞因子和内毒素水平变化的影响；3)检查既往炎症对神经激肽受体参与应激诱导的改变的影响。这些研究将有助于我们了解IBS的发病机制以及与IBD可能的异同。

DESCRIPTION (provided by applicant): Irritable Bowel Syndrome (IBS) is a chronic gastrointestinal disorder characterized by abdominal pain and altered motility. This syndrome is often confused with Inflammatory Bowel Diseases (IBD). IBD and IBS have unknown etiology, and the exact pathogenesis of both remain unknown. Stressful life events exacerbate the symptoms in both IBS and IBD. It appears that stress can change the permeability of colonic epithelium and influence the production of key regulatory cytokines. The central hypothesis of this proposal is that previous intestinal inflammation increases the susceptibility of the colonic epithelium to stress-induced permeability, enabling endotoxins to cross, bind to receptors and cause up regulation of stimulatory neurons. The specific aims of the proposed plan are to 1) measure the effects of previous intestinal inflammation on stress-induced changes en epithelial transport and membrane integrity; 2) determine the effects of previous inflammation on stress-induced changes in cytokine and endotoxin levels; 3) examine the effects of previous inflammation on the involvement of neurokinin receptors in stress-induced changes. These studies will contribute to our understanding of the mechanisms involved in IBS and the possible similarities and differences with IBD.