Petschow B W, Carter D L, Hutton G D
Mead Johnson Research Center, Bristol-Myers Squibb, Evansville, Indiana 47721.
J Pediatr Gastroenterol Nutr. 1993 Jul;17(1):49-58. doi: 10.1097/00005176-199307000-00007.
The effect of orally administered epidermal growth factor (EGF) on the mucosal growth and hydrolase activity of normal and damaged small intestine was examined in rats. Adult rats fed EGF daily at 10 times the estimated daily intake of EGF from human milk showed increases in specific activity but not total activity of various brush-border hydrolases with unaffected mucosal protein content and villus-to-crypt ratios through day 9. Ingestion of EGF for 13 days resulted in significant decreases in mucosal protein content without changes in villus height or hydrolase activity. The effect of oral EGF on recovery of damaged intestine was studied in rats fed a liquid diet supplemented with EGF at 0, 1, 10, or 20 times the estimated daily intake from human milk after treatment with methotrexate (MTX) to induce acute intestinal injury. Animals treated with MTX showed significant reductions in body weight and small intestinal villus height, mucosal protein content, and hydrolase activities through day 6 posttreatment. Daily ingestion of EGF did not affect the MTX-induced reductions in mucosal protein content and hydrolase activity by day 3 but caused significant increases in mucosal disaccharidase and leucine aminopeptidase activity by day 6 at the 1- or 10-times human milk EGF levels. Similar changes were not observed in MTX-treated rats fed the 20-times human milk level of EGF. These studies suggest that oral EGF is capable of modulating mucosal protein levels and stimulating enterocyte hydrolase expression during repair of the intestinal mucosa.
研究了口服表皮生长因子(EGF)对大鼠正常及受损小肠黏膜生长和水解酶活性的影响。成年大鼠每日摄入的EGF量为母乳中EGF估计日摄入量的10倍,至第9天,各种刷状缘水解酶的比活性增加,但总活性未变,黏膜蛋白含量及绒毛与隐窝比值未受影响。摄入EGF 13天导致黏膜蛋白含量显著降低,绒毛高度及水解酶活性无变化。在用甲氨蝶呤(MTX)诱导急性肠损伤后,研究了口服EGF对受损肠恢复的影响,给大鼠喂食添加了0、1、10或20倍母乳中EGF估计日摄入量的EGF的流质饮食。MTX处理的动物在处理后第6天体重、小肠绒毛高度、黏膜蛋白含量及水解酶活性显著降低。每日摄入EGF在第3天未影响MTX诱导的黏膜蛋白含量及水解酶活性降低,但在第6天,在1倍或10倍母乳EGF水平时,黏膜二糖酶和亮氨酸氨肽酶活性显著增加。在喂食20倍母乳EGF水平的MTX处理大鼠中未观察到类似变化。这些研究表明,口服EGF能够在肠黏膜修复过程中调节黏膜蛋白水平并刺激肠细胞水解酶表达。