Mechanisms of action of the trefoil peptides in promoting healing in models of inflammatory bowel disease

我们实验室的初步实验表明，在炎症性肠病的动物模型中，一种被称为三叶肽的小蛋白质家族的成员能够缩短溃疡的愈合时间，减少炎症。三叶肽天然存在于胃、肠和结肠中。克罗恩病和溃疡性结肠炎共同构成了人类炎症性肠病，简称IBD。它们折磨着社区的许多成员，使人虚弱，治疗费用昂贵，目前的治疗方法，如皮质类固醇和免疫系统抑制剂，有令人不快和威胁健康的副作用。因此，有充分的理由发展新的治疗形式，这些治疗形式将具有更好的耐受性，并且在其作用上具有特异性。我们相信三叶肽可能是炎症性疾病新疗法的良好候选者。本提案中概述的研究将测试最佳给药途径，以及多久给三叶肽以缓解实验性IBD的症状。此外，三叶草的有效性将与目前用于IBD治疗的其他药物进行比较，或已知可缓解炎症或加速溃疡性结肠愈合的药物。我们还将进行实验，旨在找出三叶草愈合作用的机制，最后我们将描述我们最近发现的三叶草肽家族的新成员。

Preliminary experiments from our laboratory have shown that members of a family of small proteins called trefoil peptides, found naturally in the stomach, intestine and colon, are able to shorten the healing time of ulcers and reduce inflammation, in an animal model of inflammatory bowel disease. Crohn's disease and ulcerative colitis together make up the human inflammatory bowel diseases, or IBD for short. They afflict many members of the community, are debilitating, expensive to treat, and current treatments like corticosteroids and suppressors of the immune system have unpleasant and health-threatening side effects. There are therefore good reasons for the development of new forms of therapy which will be better tolerated and which are specific in their actions. We believe that the trefoil peptides may be good candidates on which new treatments for inflammatory disease might be based. The studies outlined in this proposal will test the best route of administration, and how often to give trefoil peptides in order to relieve the symptoms of experimental IBD. In addition the effectiveness of the trefoils will be compared to other agents currently used in IBD treatment, or which are known to relieve inflammation or speed the healing of the ulcerated colon. We will also carry out experiments designed to work out the mechanisms by which the trefoils' healing effects are mediated, and finally we will characterise a new member of the trefoil peptide family which we have recently discovered.