Folkman J, Szabo S, Stovroff M, McNeil P, Li W, Shing Y
Department of Surgery, Children's Hospital, Boston, MA 02115.
Ann Surg. 1991 Oct;214(4):414-25; discussion 426-7. doi: 10.1097/00000658-199110000-00006.
The complete purification of the first angiogenic molecule, basic fibroblast growth factor (bFGF), was carried out in the authors' laboratory in 1983. Application of this peptide to chronic wounds enhances angiogenesis and accelerates wound healing. The authors showed that an acid-stable form of bFGF (i.e., bFGF-CS23) could be administered orally to rats with duodenal ulcers. The peptide promoted a ninefold increase of angiogenesis in the ulcer bed and accelerated ulcer healing more potently than cimetidine. Basic fibroblast growth factor did not reduce gastric acid. The authors now show that bFGF exists as a naturally occurring peptide in rat and human gastric and duodenal mucosa. This endogenous bFGF is present also in the bed of chronic ulcers in rats. Sucralfate binds bFGF and protects it from acid degradation. The sucralfate is angiogenic, based on its affinity for bFGF. When sucralfate is administered orally to rats, it significantly elevates the level of bFGF in the ulcer bed. Cimetidine, by its capacity to reduce gastric acid, also elevates bFGF in the ulcer bed. A hypothetical model is proposed in which prevention of ulcer formation or accelerated healing of ulcers by conventional therapies may be FGF dependent. Acid-stable bFGF-CS23 may be considered as a form of replacement therapy in the treatment of duodenal ulcers.
1983年，作者所在实验室完成了首个血管生成分子——碱性成纤维细胞生长因子（bFGF）的完全纯化。将这种肽应用于慢性伤口可促进血管生成并加速伤口愈合。作者表明，一种酸稳定形式的bFGF（即bFGF-CS23）可以口服给十二指肠溃疡大鼠。该肽使溃疡床的血管生成增加了九倍，且比西咪替丁更有效地加速了溃疡愈合。碱性成纤维细胞生长因子不会降低胃酸。作者现在表明，bFGF以天然存在的肽的形式存在于大鼠和人类的胃及十二指肠黏膜中。这种内源性bFGF也存在于大鼠慢性溃疡的溃疡床中。硫糖铝结合bFGF并保护其免受酸降解。基于其对bFGF的亲和力，硫糖铝具有血管生成作用。当给大鼠口服硫糖铝时，它会显著提高溃疡床中bFGF的水平。西咪替丁因其降低胃酸的能力，也会提高溃疡床中bFGF的水平。提出了一个假设模型，其中传统疗法预防溃疡形成或加速溃疡愈合可能依赖于FGF。酸稳定的bFGF-CS23可被视为十二指肠溃疡治疗中的一种替代疗法形式。
