Seidel E R, Haddox M K, Johnson L R
Am J Physiol. 1984 Jun;246(6 Pt 1):G649-53. doi: 10.1152/ajpgi.1984.246.6.G649.
The gastrointestinal mucosa immediately proximal to an intestinal obstruction becomes hyperplastic. Since mucosa that is distal to an obstruction atrophies, it appears that the adaptational response to obstruction is regulated by local factors. The hypothesis tested in these studies is that increased polyamine metabolism in the gut proximal to an obstruction is a required local event in the hyperplastic process. Ligation of either rat ileum or colon resulted within 66 h in a doubling of total RNA, DNA, and protein content in the 2 cm of mucosa immediately proximal to the tie. The trophic response was accompanied by an increase in primary amine content of the intestinal chyme in the segment of gut under investigation. These amines were not removed from intestinal chyme by 24 h of lyophilization, suggesting that the more volatile short-carbon-chain aliphatic amines were of limited importance. Subsequent studies focused on polyamine metabolism. Ornithine decarboxylase (ODC) activity was increased in the mucosa proximal to obstruction. In the ileum, ODC activity was increased 10-fold over control values and in the colon about 2-fold. Increased ODC activity was accompanied by corresponding increases in mucosal polyamine content. Finally, treatment of rats with difluoromethylornithine, a selective, irreversible inhibitor of ODC, partially prevented the trophic response to intestinal obstruction.
肠梗阻近端的胃肠道黏膜会发生增生。由于梗阻远端的黏膜会萎缩，因此似乎对梗阻的适应性反应是由局部因素调节的。这些研究中所检验的假设是，梗阻近端肠道中多胺代谢的增加是增生过程中必需的局部事件。结扎大鼠的回肠或结肠后，在66小时内，紧靠结扎处近端2厘米的黏膜中，总RNA、DNA和蛋白质含量增加了一倍。这种营养反应伴随着所研究肠道段中肠食糜一级胺含量的增加。经过24小时冻干处理后，这些胺并未从肠食糜中去除，这表明挥发性更强的短碳链脂肪族胺的作用有限。随后的研究集中在多胺代谢方面。梗阻近端黏膜中的鸟氨酸脱羧酶（ODC）活性增加。在回肠中，ODC活性比对照值增加了10倍，在结肠中约增加了2倍。ODC活性的增加伴随着黏膜多胺含量的相应增加。最后，用二氟甲基鸟氨酸（一种ODC的选择性、不可逆抑制剂）处理大鼠，部分地阻止了对肠梗阻的营养反应。
