Kuwayama H, Matsuo Y, Eastwood G L
Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
Am J Med. 1991 Aug 8;91(2A):15S-19S. doi: 10.1016/0002-9343(91)90446-5.
We have previously shown that chronic sucralfate ingestion stimulates gastric epithelial proliferation in rats, which may explain one of the beneficial effects of sucralfate in healing of peptic ulcers. In a separate study, we have found that chronic steroid administration delays the healing of experimental gastric ulcers in rats. This study was designed to test the beneficial effects of sucralfate, cimetidine, and lansoprazole (AG-1749, a new proton pump inhibitor), on the delayed healing by steroids in rat chronic gastric ulcers. Chronic gastric ulcers were produced in male Wistar rats, weighing 180 g, by the application of 100% acetic acid. The rats were randomly divided into five groups; (1) control, (2) vehicle alone, (3) 10 mg/kg lansoprazole, (4) 500 mg/kg sucralfate, and (5) 100 mg/kg cimetidine. Except for controls, all rats received daily intraperitoneal injections of 2.5 mg/kg hydrocortisone sodium phosphate. Tested drugs were administered intragastrically (lansoprazole and sucralfate) or intraperitoneally (cimetidine) twice a day for 2 weeks. Rats were sacrificed 14 days later and ulcer size was measured. Chronic administration of hydrocortisone sodium phosphate resulted in a significant delay of ulcer healing induced by acetic acid. Treatment with either lansoprazole or sucralfate abolished the deleterious effect of steroids, whereas cimetidine had no effect. These results indicate that lansoprazole and sucralfate overcome the delayed healing by steroids of chronic gastric ulcers in the rat.
我们之前已经表明，长期摄入硫糖铝可刺激大鼠胃上皮细胞增殖，这可能解释了硫糖铝在消化性溃疡愈合中的有益作用之一。在另一项研究中，我们发现长期给予类固醇会延迟大鼠实验性胃溃疡的愈合。本研究旨在测试硫糖铝、西咪替丁和兰索拉唑（AG - 1749，一种新型质子泵抑制剂）对类固醇导致的大鼠慢性胃溃疡愈合延迟的有益作用。通过应用100%乙酸在体重180 g的雄性Wistar大鼠中制造慢性胃溃疡。将大鼠随机分为五组：（1）对照组，（2）仅给予赋形剂组，（3）10 mg/kg兰索拉唑组，（4）500 mg/kg硫糖铝组，和（5）100 mg/kg西咪替丁组。除对照组外，所有大鼠每天腹腔注射2.5 mg/kg氢化可的松磷酸钠。受试药物通过胃内给药（兰索拉唑和硫糖铝）或腹腔内给药（西咪替丁），每天两次，共2周。14天后处死大鼠并测量溃疡大小。长期给予氢化可的松磷酸钠导致乙酸诱导的溃疡愈合显著延迟。用兰索拉唑或硫糖铝治疗可消除类固醇的有害作用，而西咪替丁则无作用。这些结果表明，兰索拉唑和硫糖铝可克服类固醇导致的大鼠慢性胃溃疡愈合延迟。
