Fitzpatrick L R, Jakubowska A, Martin G E, Davis M, Jaye M C, Dionne C A
Pharmacology Department, Rhône-Poulenc Rorer Central Research, Collegeville, Pa 19426-0107.
Digestion. 1992;53(1-2):17-27. doi: 10.1159/000200967.
Acidic fibroblast growth factor (aFGF) was evaluated for the healing of acetic-acid-induced gastric ulcers in rats. The effect of aFGF on angiogenesis in the gastric ulcer bed was determined by the carmine dye infusion method, while its effect on gastric acid secretion was assessed in chronic gastric fistula rats. Oral treatment with aFGF, in the presence of heparin, reduced (ED50 value = 30.2 micrograms/kg/day) the acetic-acid-induced gastric ulcer area, when assessed 1 week later. aFGF was about 1,333-fold more potent than famotidine for healing such ulcers. At a dose of 200 micrograms/kg/day, aFGF increased the carmine density 3-fold and correspondingly reduced (80%) the gastric ulcer area. Thus, the ulcer healing effect of this agent involves angiogenesis in the gastric ulcer bed. This effect of aFGF appears to be unrelated to an inhibition of gastric acid secretion, as it was ineffective in chronic gastric fistula rats. In summary, oral aFGF significantly accelerates the healing of experimental gastric ulcers in rats. It may be a potent and effective agent for the treatment of peptic ulcers in humans.
评估了酸性成纤维细胞生长因子(aFGF)对大鼠乙酸诱导胃溃疡愈合的作用。采用胭脂红染料注入法测定aFGF对胃溃疡创面血管生成的影响,同时在慢性胃瘘大鼠中评估其对胃酸分泌的影响。在肝素存在的情况下,口服aFGF(ED50值 = 30.2微克/千克/天)可减少乙酸诱导的胃溃疡面积,在1周后进行评估时可见此效果。aFGF愈合此类溃疡的效力比法莫替丁高约1333倍。在剂量为200微克/千克/天时,aFGF使胭脂红密度增加3倍,并相应减少(80%)胃溃疡面积。因此,该药物的溃疡愈合作用涉及胃溃疡创面的血管生成。aFGF的这种作用似乎与胃酸分泌抑制无关,因为在慢性胃瘘大鼠中其作用无效。总之,口服aFGF可显著加速大鼠实验性胃溃疡的愈合。它可能是治疗人类消化性溃疡的一种强效且有效的药物。