Erickson R A, Bezabah S, Jonas G, Lifrak E, Tarnawski A S
Department of Medicine, Department of Veterans Affairs Medical Center, Long Beach, California 90822.
Dig Dis Sci. 1991 Jul;36(7):897-904. doi: 10.1007/BF01297138.
To test whether omeprazole would increase the susceptibility of the duodenum to damage, 200 to 250-g male Sprague-Dawley rats were given 10 mg/kg of omeprazole (Losec) by gavage every morning for 29 days. Control rats were given gavage buffer alone. After fasting overnight, half the rats received 10 mg/kg indomethacin intraperitoneally; then all rats were given 2 ml of 50% ethanol by gavage. Three hours later the rats were killed and the stomach and duodenum removed and histologic injury to the duodenal mucosal was quantitated. In omeprazole pretreated rats, gavage with ethanol resulted in a significant twofold worsening of duodenal injury. Pretreatment with indomethacin to decrease endogenous prostaglandin production resulted in more severe ethanol-induced duodenal injury in both groups; however, there were no longer statistically significant differences between the omeprazole and control groups. Measurement of duodenal mucosal synthesis of prostaglandin E2 showed no difference between the omeprazole and control groups. Thus chronic administration of omeprazole appears to increase the susceptibility of the duodenal mucosa to ethanol injury in rats. The mechanism of this effect is as yet unknown but does not appear to be prostaglandin-mediated.
为了测试奥美拉唑是否会增加十二指肠对损伤的易感性，将体重200至250克的雄性Sprague-Dawley大鼠每天早晨经口灌胃给予10毫克/千克奥美拉唑（洛赛克），持续29天。对照大鼠仅给予灌胃缓冲液。禁食过夜后，一半大鼠腹腔注射10毫克/千克吲哚美辛；然后所有大鼠经口灌胃给予2毫升50%乙醇。3小时后处死大鼠，取出胃和十二指肠，对十二指肠黏膜的组织学损伤进行定量分析。在经奥美拉唑预处理的大鼠中，灌胃乙醇导致十二指肠损伤显著加重两倍。用吲哚美辛预处理以降低内源性前列腺素的产生，导致两组中乙醇诱导的十二指肠损伤更严重；然而，奥美拉唑组和对照组之间不再有统计学上的显著差异。十二指肠黏膜前列腺素E2合成的测量结果显示，奥美拉唑组和对照组之间没有差异。因此，长期给予奥美拉唑似乎会增加大鼠十二指肠黏膜对乙醇损伤的易感性。这种作用的机制尚不清楚，但似乎不是由前列腺素介导的。
