Thompson J S, Saxena S K, Sharp J G
Omaha Veterans Administration Medical Center, Nebraska.
J Surg Res. 1988 May;44(5):589-95. doi: 10.1016/0022-4804(88)90166-7.
Urogastrone (UG) stimulates the growth of intestinal neomucosa on patched intestinal defects. This effect may be dependent on increased polyamine biosynthesis. The aim of this study was to determine if difluoromethylornithine (DFMO), a specific inhibitor of polyamine synthesis, would inhibit urogastrone stimulation of neomucosal growth. Twenty-four New Zealand white rabbits (2.1-2.9 kg) had 2 x 5-cm ileal defects patched with adjacent cecal serosal surface. Group I (n = 6) served as controls. Group II (n = 6) received UG 1.5 micrograms/kg/hr subcutaneously. Group III (n = 6) took 2% DFMO orally. Group IV (n = 6) received the same doses of UG and DFMO simultaneously. Animals were sacrificed 7 days after patching to assess neomucosal growth. Urogastrone infusion resulted in significantly greater neomucosal coverage (54 +/- 4%) and neomucosal surface area (236 +/- 18 mm2) in the Group II animals. Neomucosal coverage and contraction of the intestinal defects and neomucosal surface area were similar in the other three groups. Crypt cell production rate (15.5 +/- 2.0 cells/hr) and disaccharidase activity were also significantly greater in Group II than in the other groups. DFMO alone (Group III) resulted in a significantly lower ornithine decarboxylase (ODC) activity, polyamine content, and crypt cell production rate. Group IV animals had lower ODC activity but not lower polyamine content or crypt cell production rate. UG resulted in a significant increase in neomucosal growth. DFMO prevented this stimulatory effect and inhibited ornithine decarboxylase activity. The stimulation of neomucosal growth by UG is dependent, at least in part, on increased polyamine biosynthesis.
尿抑胃素（UG）可刺激修补后的肠缺损处新生肠黏膜的生长。这种作用可能依赖于多胺生物合成的增加。本研究的目的是确定多胺合成的特异性抑制剂二氟甲基鸟氨酸（DFMO）是否会抑制尿抑胃素对新生黏膜生长的刺激作用。24只新西兰白兔（体重2.1 - 2.9千克）的2处5厘米回肠缺损用相邻的盲肠浆膜表面进行修补。第一组（n = 6）作为对照。第二组（n = 6）皮下注射1.5微克/千克/小时的UG。第三组（n = 6）口服2%的DFMO。第四组（n = 6）同时接受相同剂量的UG和DFMO。修补后7天处死动物以评估新生黏膜生长情况。第二组动物中，输注尿抑胃素导致新生黏膜覆盖面积（54±4%）和新生黏膜表面积（236±18平方毫米）显著增大。其他三组的新生黏膜覆盖面积、肠缺损收缩情况及新生黏膜表面积相似。第二组的隐窝细胞生成率（15.5±2.0个细胞/小时）和双糖酶活性也显著高于其他组。单独使用DFMO（第三组）导致鸟氨酸脱羧酶（ODC）活性、多胺含量和隐窝细胞生成率显著降低。第四组动物的ODC活性较低，但多胺含量和隐窝细胞生成率并未降低。UG导致新生黏膜生长显著增加。DFMO可阻止这种刺激作用并抑制鸟氨酸脱羧酶活性。尿抑胃素对新生黏膜生长的刺激作用至少部分依赖于多胺生物合成的增加。
