Greenwood-Van Meerveld B, Venkova K, Connolly K
Oklahoma Foundation for Digestive Research, Basic Science Laboratories, Veterans Administration Medical Center, Room 151, 921 NE 13th Street, Oklahoma City, OK 73104, USA.
J Pharm Pharmacol. 2003 Jan;55(1):67-75. doi: 10.1111/j.2042-7158.2003.tb02435.x.
Human keratinocyte growth factor-2 (KGF-2) is a member of the fibroblast growth factor family that promotes healing of experimental small intestinal ulceration and colitis. The aim of this study was to determine whether repifermin, a truncated form of recombinant human KGF-2, reverses abnormalities in colonic mucosal transport in a murine model of dextran sulfate sodium (DSS)-induced colitis. Male Swiss-Webster mice were given 4% DSS in drinking water for 7 days and then normal drinking water for 3 days. Repifermin (5 mg kg(-1), i.p.) or vehicle was administered daily for 7 days starting on Day 4 of DSS exposure. On Day 10, net ion transport was measured electrophysiologically in colonic mucosal sheets. Repifermin significantly reduced DSS-induced colonic inflammation measured by tissue myeloperoxidase activity. Concurrently, in colonic tissue taken from mice treated with repifermin, there was a normalization of basal potential difference and short circuit current, and an improvement in the secretory responses to stimulation of muscarinic and ganglionic cholinoceptors. In control mice, repifermin did not interact directly with colonic epithelial cells or intramural neurones to induce immediate changes in net electrogenic transport. The results suggest that repifermin therapy may improve the mucosal electrogenic transport that is impaired during colitis.
人角质形成细胞生长因子-2（KGF-2）是成纤维细胞生长因子家族的一员，可促进实验性小肠溃疡和结肠炎的愈合。本研究的目的是确定重组人KGF-2的截短形式瑞匹凡明是否能逆转葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎模型中结肠黏膜转运的异常。给雄性瑞士韦伯斯特小鼠饮用含4% DSS的水7天，然后饮用正常水3天。从DSS暴露第4天开始，每天腹腔注射瑞匹凡明（5 mg·kg⁻¹）或赋形剂，持续7天。在第10天，用电生理学方法测量结肠黏膜片的净离子转运。瑞匹凡明显著降低了通过组织髓过氧化物酶活性测量的DSS诱导的结肠炎症。同时，在用瑞匹凡明治疗的小鼠的结肠组织中，基础电位差和短路电流恢复正常，对毒蕈碱和神经节胆碱能受体刺激的分泌反应有所改善。在对照小鼠中，瑞匹凡明不与结肠上皮细胞或壁内神经元直接相互作用以诱导净电转运的立即变化。结果表明，瑞匹凡明治疗可能改善结肠炎期间受损的黏膜电转运。
