Luck M S, Bass P
School of Pharmacy, University of Wisconsin-Madison.
J Pharmacol Exp Ther. 1993 Feb;264(2):984-90.
The effect of epidermal growth factor on the rate of healing was examined in a rat model of colitis. Ulceration and inflammation of the distal colon were induced by a single intracolonic administration of 0.25 ml of 30% ethanol containing 30 mg of trinitrobenzenesulfonic acid. Epidermal growth factor was delivered intracolonically via the rectum or s.c. for 7 days after induction of colitis. Repeated s.c. injections of epidermal growth factor (25 and 100 micrograms/kg/12 hr) or continuous s.c. delivery with Alzet osmotic pumps (50 and 200 micrograms/kg/24 hr) significantly reduced colonic ulceration and inflammation. Epidermal growth factor significantly reduced myeloperoxidase activity in colonic tissue and there was restitution of the glandular mucosa after epidermal growth factor treatment. In contrast, daily intracolonic treatment with epidermal growth factor (25, 100 and 200 micrograms/kg/24 hr) did not significantly reduce the colonic damage. However, intracolonic delivery of 5-aminosalicylic acid (100 and 200 mg/kg/24 hr) dose-dependently reduced the colonic damage as assessed macroscopically and histologically. We conclude that systemic and not intracolonic administration of epidermal growth factor can accelerate healing of colonic ulceration and is effective in reducing inflammation in this model of colitis.
在大鼠结肠炎模型中研究了表皮生长因子对愈合速度的影响。通过在结肠内单次给予0.25 ml含30 mg三硝基苯磺酸的30%乙醇诱导远端结肠溃疡和炎症。在结肠炎诱导后,通过直肠或皮下途径向结肠内递送表皮生长因子,持续7天。重复皮下注射表皮生长因子(25和100微克/千克/12小时)或用Alzet渗透泵持续皮下递送(50和200微克/千克/24小时)可显著减轻结肠溃疡和炎症。表皮生长因子显著降低结肠组织中的髓过氧化物酶活性,且在表皮生长因子治疗后腺性黏膜得以修复。相比之下,每日通过结肠内给予表皮生长因子(25、100和200微克/千克/24小时)并未显著减轻结肠损伤。然而,通过结肠内递送5-氨基水杨酸(100和200毫克/千克/24小时)在宏观和组织学评估中均呈剂量依赖性地减轻结肠损伤。我们得出结论,在该结肠炎模型中,表皮生长因子经全身给药而非结肠内给药可加速结肠溃疡的愈合并有效减轻炎症。