Satoh H, Shino A, Sato F, Asano S, Murakami I, Inatomi N, Nagaya H, Kato K, Szabo S, Folkman J
Pharmaceutical Research Division, Takeda Chemical Industries, Ltd., Yodogawa-ku, Osaka, Japan.
Jpn J Pharmacol. 1997 Jan;73(1):59-71. doi: 10.1254/jjp.73.59.
Recently, it has been pointed out that growth factors play an important role in the healing of gastrointestinal ulcers. In the present study, we examined the role of endogenous basic fibroblast growth factor (bFGF) in the healing of gastric ulcers in the rat. In male SD rats, gastric ulcers were induced in the antrum by injection of acetic acid. Time-dependent changes in the area and bFGF content in the ulcerated area and distribution of bFGF in the ulcerated mucosa were examined. Effects of bFGF mutein CS23 (TGP-580) and a monoclonal antibody for bFGF (MAb 3H3) on the healing of the gastric ulcers and angiogenesis in the ulcer bed were also examined. The content of bFGF in the ulcerated area increased with time as the ulcer healed and reached a maximum 7 days after ulcer formation. In the gastric ulcer bed, many cells such as fibroblasts and macrophages were positively stained immunohistochemically by anti-bFGF antiserum. MAb 3H3 (0.1 mg/rat/day, i.v.) inhibited angiogenesis in the ulcer bed and significantly delayed ulcer healing, while TGP-580 (0.001-0.1 mg/kg x 2/day, p.o.) increased the number of microvessels in the ulcer bed and accelerated the healing. These results suggest that endogenous bFGF may play an important role in the healing of gastric ulcers in the rat and that the angiogenic properties of bFGF (TGP-580) may be involved in its effect on ulcer healing.
最近,有人指出生长因子在胃肠道溃疡愈合中起重要作用。在本研究中,我们检测了内源性碱性成纤维细胞生长因子(bFGF)在大鼠胃溃疡愈合中的作用。在雄性SD大鼠中,通过注射乙酸在胃窦诱导胃溃疡。检测溃疡面积和溃疡区域bFGF含量的时间依赖性变化以及bFGF在溃疡黏膜中的分布。还检测了bFGF突变体CS23(TGP - 580)和bFGF单克隆抗体(MAb 3H3)对胃溃疡愈合和溃疡床血管生成的影响。随着溃疡愈合,溃疡区域的bFGF含量随时间增加,并在溃疡形成后7天达到最大值。在胃溃疡床,许多细胞如成纤维细胞和巨噬细胞被抗bFGF抗血清免疫组化阳性染色。MAb 3H3(0.1mg/大鼠/天,静脉注射)抑制溃疡床血管生成并显著延迟溃疡愈合,而TGP - 580(0.001 - 0.1mg/kg×2/天,口服)增加溃疡床微血管数量并加速愈合。这些结果表明内源性bFGF可能在大鼠胃溃疡愈合中起重要作用,并且bFGF(TGP - 580)的血管生成特性可能与其对溃疡愈合的作用有关。