Poulsom R, Begos D E, Modlin I M
Histopathology Unit, Imperial Cancer Research Fund, London, United Kingdom.
Yale J Biol Med. 1996 Mar-Apr;69(2):137-46.
Healing of mucosal damage takes place in two phases: restitution of mucosal integrity and remodeling towards recreating the original glandular arrangements. These processes can be observed in several experimental rodent models: e.g., cryoprobe or NSAID-generated ulcers in the gastric or duodenal mucosa and following surgical resection of the small or large bowel. In some studies, it has been possible to detect changes in the expression of peptides, either in the reparative epithelium or adjacent to the damage, that may contribute to the healing processes. Trefoil peptides are expressed constitutively by epithelial cells in specific regions of the gastrointestinal tract, in association with mucins. Several studies have shown that trefoil peptide expression is enhanced at sites of damage in man and rat, and experimental evidence supports their active participation in the healing process. Recombinant trefoil peptides are able to enhance the rate of epithelial cell migration in vitro and are able to protect against indomethacin-induced damage in vivo, yet they do not depend upon TGF-beta for enhancing cell migration and do not appear to affect acid secretion. The mode of action of trefoil peptides appears to be receptor-mediated but is not simple. There is good evidence that there are interactions between members of the trefoil family and the EGF family that are beneficial for mucosal defense and repair. This raises the possibility that combining trefoil peptides with other growth factors or small molecules may be advantageous for treatment of ulceration.
黏膜完整性的恢复以及向重建原始腺体结构的重塑过程。这些过程可在多种实验性啮齿动物模型中观察到，例如，胃或十二指肠黏膜的冷冻探头或非甾体抗炎药所致溃疡，以及小肠或大肠手术切除后。在一些研究中，已能够检测到修复上皮或损伤部位附近肽表达的变化，这些变化可能有助于愈合过程。三叶肽由胃肠道特定区域的上皮细胞与黏蛋白共同组成性表达。多项研究表明，三叶肽在人和大鼠的损伤部位表达增强，实验证据支持它们积极参与愈合过程。重组三叶肽能够在体外提高上皮细胞迁移速率，并在体内预防吲哚美辛诱导的损伤，但它们增强细胞迁移并不依赖于转化生长因子-β，且似乎不影响胃酸分泌。三叶肽的作用方式似乎是受体介导的，但并非简单的方式。有充分证据表明，三叶肽家族成员与表皮生长因子家族成员之间存在相互作用，这对黏膜防御和修复有益。这增加了将三叶肽与其他生长因子或小分子联合使用可能有利于溃疡治疗的可能性。
