Wang J Y, Johnson L R
Department of Physiology and Biophysics, University of Tennessee Medical School, Memphis.
Gastroenterology. 1992 Apr;102(4 Pt 1):1109-17.
The purpose of this study was to examine whether luminal polyamines administered exogenously accelerate the repair of stress-induced intestinal mucosal damage in rats. 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 4, 12, and 24 hours thereafter. Duodenal mucosa was examined histologically, and ornithine decarboxylase activity and polyamine levels were measured. Repair of duodenal mucosa after stress was extensively delayed by administering 500 mg/kg DL-alpha-difluoromethylornithine (DFMO) IP. DFMO also inhibited ornithine decarboxylase activity and prevented increases in duodenal mucosal polyamine content. Intragastric administration of the polyamines, putrescine, spermidine, and spermine (100 mg/kg), immediately after stress significantly prevented the decreased rate of repair caused by DFMO. Spermidine or spermine accelerated healing better than putrescine in the DFMO-treated rats. Spermine also significantly increased the normal rate of repair of stress-induced damage. The delayed recovery of mucosal DNA, RNA, and protein content following stress in the DFMO-treated rats was prevented by exogenous polyamines. The reduced levels of duodenal mucosal spermidine and spermine in stressed rats treated with DFMO returned toward control levels after administration of exogenous spermidine. These results indicate that (a) luminal polyamines effectively substitute for endogenously synthesized polyamines in the repair process of the duodenal mucosa, (b) luminal polyamines can increase the normal healing rate and, (c) polyamines accelerate healing by increasing both an early phase and a later phase dependent on cell renewal.
本研究的目的是检验外源性给予肠腔多胺是否能加速应激诱导的大鼠肠黏膜损伤的修复。大鼠禁食22小时，置于束缚笼中，并将其浸入水中至剑突水平6小时。在应激期结束后立即处死动物，或在此后4、12和24小时处死。对十二指肠黏膜进行组织学检查，并测量鸟氨酸脱羧酶活性和多胺水平。腹腔注射500mg/kg DL-α-二氟甲基鸟氨酸（DFMO）可显著延迟应激后十二指肠黏膜的修复。DFMO还抑制鸟氨酸脱羧酶活性，并阻止十二指肠黏膜多胺含量的增加。应激后立即灌胃给予多胺腐胺、亚精胺和精胺（100mg/kg）可显著防止DFMO引起的修复速率降低。在DFMO处理的大鼠中，亚精胺或精胺比腐胺更能加速愈合。精胺还显著提高了应激诱导损伤的正常修复速率。外源性多胺可防止DFMO处理的大鼠应激后黏膜DNA、RNA和蛋白质含量的延迟恢复。给予外源性亚精胺后，DFMO处理的应激大鼠十二指肠黏膜亚精胺和精胺水平降低，恢复至对照水平。这些结果表明：（a）肠腔多胺在十二指肠黏膜修复过程中可有效替代内源性合成的多胺；（b）肠腔多胺可提高正常愈合速率；（c）多胺通过增加依赖细胞更新的早期和晚期阶段来加速愈合。
