Therapeutic effects of rectal administration of basic fibroblast growth factor on experimental murine colitis
Therapeutic effects of rectal administration of basic fibroblast growth factor on experimental murine colitis
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DOI：
10.1053/j.gastro.2005.01.006
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发表时间：
2005-04-01
期刊：
影响因子：
29.4
通讯作者：
Chiba, T
中科院分区：
文献类型：
--
作者：
Matsuura, M;Okazaki, K;Chiba, T
背景与目的：碱性成纤维细胞生长因子（bFGF）是一种有前途的治疗多种疾病的药物。然而，bFGF 是否能有效治疗炎症性肠病仍不清楚。本研究的目的是检验 bFGF 对 2 个实验性小鼠结肠炎模型的功效并探讨其分子机制。方法：我们评估了人重组bFGF（hrbFGF）对右旋糖酐硫酸钠（DSS）诱导的结肠炎小鼠和三硝基苯磺酸（TNBS）诱导的结肠炎小鼠以及正常小鼠的影响。检查体重、存活率和结肠组织的组织学结果。测定结肠组织中肿瘤坏死因子（TNF）-α、环氧合酶（COX）-2、转化生长因子（TGF）-β、粘蛋白2（MUC2）、肠三叶因子（ITF）和血管内皮生长因子（VEGF）的基因表达。通过免疫组织化学评价hrbFGF对结肠上皮细胞的增殖活性。结果：直肠施用 hrbFGF 以剂量依赖性方式改善 DSS 诱导的结肠炎。用 hrbFGF 治疗的 DSS 诱导结肠炎小鼠的结肠组织中 TNIF-α 基因表达显着降低，而 MUC2 和 ITF 信使 RNA 表达上调。直肠给予 hrbFGF 显着提高了患有 TNBS 诱导结肠炎和部分改善结肠炎的小鼠的存活率。 hrbFGF显着增加正常小鼠结肠上皮中Ki-67阳性细胞的数量，并上调结肠组织中COX-2、TGF-β、MUC2、ITF和VEGF的基因表达。结论：bFGF 直肠给药可能是治疗炎症性肠病的一种有前景的选择。
Background & Aims: Basic fibroblast growth factor (bFGF) is a promising therapeutic agent for various diseases. It remains unclear, however, whether bFGF is effective for the treatment of inflammatory bowel disease. The aim of this study was to examine the efficacy of bFGF on 2 experimental murine colitis models and to investigate its molecular mechanisms. Methods: We evaluated the effects of human recombinant bFGF (hrbFGF) on mice with dextran sulfate sodium (DSS)induced colitis and mice with trinitrobenzene sulfonic acid (TNBS)-induced colitis as well as normal mice. Body weight, survival rate, and histologic findings of the colonic tissues were examined. Gene expression of tumor necrosis factor (TNF)-alpha, cyclooxygenase (COX)-2, transforming growth factor (TGF)-beta, mucin 2 (MUC2), intestinal trefoil factor (ITF), and vascular endothelial growth factor (VEGF) in the colonic tissues was determined. The proliferation activity of hrbFGF on the colonic epithelium was evaluated by immunohistochemistry. Results: Rectal administration of hrbFGF ameliorated DSS-induced colitis in a dose-dependent manner. Gene expression of TNIF-alpha was significantly reduced in the colonic tissues of mice with DSS-induced colitis treated with hrbFGF, whereas MUC2 and ITF messenger RNA expression was up-regulated. Rectal administration of hrbFGF significantly improved the survival rate of mice with TNBS-induced colitis and partially ameliorated colitis. hrbFGF significantly increased the number of Ki-67-positive cells in the colonic epithelium of normal mice, and up-regulated the gene expression of COX-2, TGF-beta, MUC2, ITF, and VEGF in the colonic tissues. Conclusions: Rectal administration of bFGF might be a promising option for the treatment of inflammatory bowel disease.