Zeeh J M, Procaccino F, Hoffmann P, Aukerman S L, McRoberts J A, Soltani S, Pierce G F, Lakshmanan J, Lacey D, Eysselein V E
Inflammatory Bowel Disease Center, Division of Gastroenterology, Harbor-UCLA Medical Center, Torrance, California, USA.
Gastroenterology. 1996 Apr;110(4):1077-83. doi: 10.1053/gast.1996.v110.pm8612996.
BACKGROUND & AIMS: Keratinocyte growth factor (KGF) is known to enhance tissue repair in the skin; however, its role in the gastrointestinal tract is largely unknown. The aim of this study was to evaluate the effects of exogenous KGF in an experimental model of colitis in rats.
KGF was administered before or after induction of colitis with 2,4,6-trinitrobenzenesulfonic acid/ethanol. In the first two study groups, KGF (5 mg/kg) was administered intraperitoneally 24 hours and 1 hour before induction of colitis; animals were killed 8 hours (n=10) and 1 week (n=10) after injury. In subsequent study groups, KGF or vehicle treatment was begun 24 hours after the induction of colitis at doses of 5 (n=20), 1 (n=10), and 0.1 (n=10) mg/kg intraperitoneally and continued once daily for 1 week. Colonic tissue samples were evaluated macroscopically and microscopically for mucosal injury and assayed for myeloperoxidase activity.
Administration of KGF after but not before induction of colitis significantly ameliorated tissue damage. Macroscopic necrosis and microscopic ulcerations were reduced by 40%-50% at KGF doses of 1 and 5 mg/kg.
Exogenous KGF has a key role in mucosal healing in an experimental model of colitis in rats.
已知角质形成细胞生长因子(KGF)可促进皮肤组织修复;然而,其在胃肠道中的作用在很大程度上尚不清楚。本研究的目的是评估外源性KGF在大鼠结肠炎实验模型中的作用。
在用2,4,6-三硝基苯磺酸/乙醇诱导结肠炎之前或之后给予KGF。在前两个研究组中,在诱导结肠炎前24小时和1小时腹腔注射KGF(5mg/kg);在损伤后8小时(n = 10)和1周(n = 10)处死动物。在随后的研究组中,在诱导结肠炎后24小时开始腹腔注射KGF或赋形剂,剂量分别为5(n = 20)、1(n = 10)和0.1(n = 10)mg/kg,每天1次,持续1周。对结肠组织样本进行大体和显微镜下评估,以观察黏膜损伤情况,并检测髓过氧化物酶活性。
在诱导结肠炎后而非之前给予KGF可显著改善组织损伤。在KGF剂量为1和5mg/kg时,大体坏死和显微镜下溃疡减少了40%-50%。
外源性KGF在大鼠结肠炎实验模型的黏膜愈合中起关键作用。