Wang J Y, Johnson L R
Department of Physiology and Biophysics, University of Tennessee Medical School, Memphis.
Gastroenterology. 1991 Feb;100(2):333-43. doi: 10.1016/0016-5085(91)90200-5.
This investigation shows whether polyamines and ornithine decarboxylase have a role in duodenal mucosal repair following stress-induced microscopic damage. Rats were fasted for 22 hours, placed in restraint cages, and immersed in water to the xiphoid process for 6 hours. Animals were killed either immediately after the period of stress or at 2-hour intervals up to 24 hours thereafter. Duodenal mucosa was examined histologically, and ornithine decarboxylase and polyamine levels were measured. Ornithine decarboxylase activity was increased significantly up to 6 hours following stress, peaking at 4 hours at a level 10 times the prestress control. By 8 hours, enzyme activity had returned to near normal. Increases in mucosal putrescine, spermidine, and spermine content paralleled the changes in ornithine decarboxylase activity and peaked 4 hours after stress. Stress resulted in microscopic damage evidenced by a nearly complete absence of villi. Significant macroscopic lesions were not present following stress. Mucosal repair was evident 12 hours after stress and almost complete by 24 hours, although the restituted villi were short and blunted. The decreases in mucosal DNA, RNA, and protein content caused by stress were restored and reached near-normal levels 12 hours after the period of stress. In animals given the specific inhibitor of ornithine decarboxylase, alpha-difluoromethylornithine, increases in duodenal mucosal ornithine decarboxylase activity and polyamine levels were inhibited and mucosal repair was almost completely prevented following stress. alpha-Difluoromethylornithine also prevented the recovery of DNA, RNA, and protein content of the duodenal mucosa. These results indicate that duodenal mucosal damage following stress is repaired rapidly; the repair process is accompanied by significant increases in ornithine decarboxylase activity and polyamine levels; and the increases in ornithine decarboxylase and polyamines are absolutely required for the normal repair of the mucosa.
本研究旨在探究多胺和鸟氨酸脱羧酶在应激诱导的微观损伤后十二指肠黏膜修复过程中是否发挥作用。将大鼠禁食22小时，置于束缚笼中，并浸入水中至剑突水平6小时。应激期结束后立即处死动物，或在此后每隔2小时处死一批，直至24小时。对十二指肠黏膜进行组织学检查，并测定鸟氨酸脱羧酶和多胺水平。应激后6小时内，鸟氨酸脱羧酶活性显著升高，在4小时达到峰值，为应激前对照水平的10倍。到8小时时，酶活性已恢复至接近正常水平。黏膜中腐胺、亚精胺和精胺含量的增加与鸟氨酸脱羧酶活性的变化平行，并在应激后4小时达到峰值。应激导致微观损伤，表现为绒毛几乎完全缺失。应激后未出现明显的宏观病变。应激12小时后黏膜修复明显，到24小时时几乎完全修复，尽管修复后的绒毛短而钝。应激导致的黏膜DNA、RNA和蛋白质含量的降低在应激期结束12小时后恢复并达到接近正常水平。在给予鸟氨酸脱羧酶特异性抑制剂α-二氟甲基鸟氨酸的动物中，十二指肠黏膜鸟氨酸脱羧酶活性和多胺水平的升高受到抑制，应激后黏膜修复几乎完全被阻止。α-二氟甲基鸟氨酸还阻止了十二指肠黏膜DNA、RNA和蛋白质含量的恢复。这些结果表明，应激后十二指肠黏膜损伤修复迅速；修复过程伴随着鸟氨酸脱羧酶活性和多胺水平的显著升高；鸟氨酸脱羧酶和多胺的升高是黏膜正常修复所绝对必需的。
