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Accelerated Ulcer Healing via Activation of Endogenous Tissue Repairing Factors by Sulfated Cyclic Oligosaccharides

硫酸化环状低聚糖激活内源性组织修复因子加速溃疡愈合

基本信息

批准号：
08672563
负责人：
IRIE Tetsumi
金额：
$ 1.41万
依托单位：
Kumamoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08672563/
关键词：
cyclodextrin sulfated cyclic oligosaccharide water-insoluble aluminium salt endogenous tissue repairing factor basic fibroblast growth factor enzymatic stability intestinal mucosal erosion 細胞増殖因子難水溶性塩形成

项目摘要

Tissue repairing factors including basic fibroblast growth factor (bFGF) exist as naturally occurring peptides in gastric and duodenal mucosa, and they nay act to prevent ulceration unless these peptides are excessively degraded by gastric juices. The objective of this study, thesefore, is to investigate the potential use of water-insoluble aluminium salts of sulfated cyclic oligosaccharides for modulating the tissue repairing factors. The results obtained were as follows.1. Sulfated cyclic oligosaccharides had a high affinity for bFGF and protect it from proteolytic degradation. These sulfated cyclic oligosaccharides may electrosatically bind close to the putative heparin binding domain, a cluster of several basic amino acid residues, on the surface of the bFGF molecule.2. The mitogenic activity of bFGF released from its adsorbate with aluminium salts of sulfated cyclic oligosaccharides was almost comparable with thay of the intact protein, as indicated by the proliferation of kidney cells of baby hamsters (BHK-21) .3. The oral administration of alminium salts of sulfated cyclic oligosaccharides tended to enhance the healing rate of aceticacid-induced gastric ulcers and cysteamine-inducedduodenal ulcers. In particular, the aluminium salts of sulfated cyclic oligosaccharides loaded with bFGF had the most prominent healing effects on the ulcers.These results suggest that the aluminium salts of sulfated cyclic oligosaccharides have a potent therapeutice efficacy for wound healing via stabilization of endogenous tissue repairing factors and can be applicable to the treatment of intestinal mucosal erosions.

包括碱性成纤维细胞生长因子（bFGF）在内的组织修复因子以天然肽的形式存在于胃和十二指肠粘膜中，除非这些肽被胃液过度降解，否则它们可以起到预防溃疡的作用。因此，本研究的目的是研究水不溶性硫酸环寡糖铝盐用于调节组织修复因子的潜在用途。主要研究结果如下：1.硫酸化环状寡糖对bFGF有很高的亲和力，并保护其免受蛋白水解降解。这些硫酸化的环状寡糖可以与bFGF分子表面上的假定的肝素结合结构域（几个碱性氨基酸残基的簇）电结合。碱性成纤维细胞生长因子（bFGF）的促有丝分裂活性与完整蛋白质的促有丝分裂活性几乎相当，如幼仓鼠（BHK-21）肾细胞增殖所示.口服硫酸环寡糖的丙氨酸盐倾向于提高乙酸诱导的胃溃疡和半胱胺诱导的十二指肠溃疡的愈合率。特别是碱性成纤维细胞生长因子负载的硫酸环寡糖铝盐对溃疡的愈合效果最为显著，提示硫酸环寡糖铝盐通过稳定内源性组织修复因子而具有较强的促进伤口愈合的作用，可用于肠粘膜糜烂的治疗。