Wagner K A, Nandi J, King R L, Levine R A
Department of Medicine, State University of New York Health Science Center, Syracuse 13210.
Dig Dis Sci. 1995 Jan;40(1):134-40. doi: 10.1007/BF02063956.
The effects of nonsteroidal antiinflammatory drugs on ulcerogenesis and gastric secretion were evaluated in a pylorus-ligated rat model. Oral administration of salicylate (50 mg/kg), aspirin (50 mg/kg), and indomethacin (3.5 mg/kg) significantly increased ulcerogenesis over the basal value by six- to sevenfold, but ibuprofen's (10 mg/kg) fourfold increase was not significant. Aspirin in conjunction with histamine (0.5 mg/kg subcutaneously) significantly increased ulcerogenesis by 2.7-fold compared to histamine alone. Basal acid secretion was increased significantly by 156% after indomethacin, but not by other nonsteroidal antiinflammatory drugs. In contrast, all nonsteroidal antiinflammatory drugs, except indomethacin, significantly decreased histamine-stimulated acid secretion. Non-steroidal antiinflammatory drugs had no effect on pepsinogen secretion. Ranitidine pretreatment (25 mg/kg intraperitoneally) significantly decreased basal acid and pepsinogen secretion in all treatment groups by > 85% and > 40%, respectively, and ulcerations induced by salicylate, aspirin, and indomethacin were also inhibited by 90%, 60%, and 60%, respectively. The observed inhibition of prostaglandin E2 generation by nonsteroidal antiinflammatory drugs under basal secretory conditions appeared to correlate with the extent of ulcerogenesis. Our data support the concept that acid, in addition to inhibition of prostaglandin E2 synthesis, plays an important role in the pathogenesis of nonsteroidal antiinflammatory drug-induced gastropathy.
在幽门结扎大鼠模型中评估了非甾体抗炎药对溃疡形成和胃分泌的影响。口服水杨酸盐（50毫克/千克）、阿司匹林（50毫克/千克）和吲哚美辛（3.5毫克/千克）使溃疡形成率较基础值显著增加了6至7倍，但布洛芬（10毫克/千克）4倍的增加并不显著。与单独使用组胺相比，阿司匹林联合组胺（皮下注射0.5毫克/千克）使溃疡形成率显著增加了2.7倍。吲哚美辛使基础胃酸分泌显著增加了156%，但其他非甾体抗炎药没有这种作用。相反，除吲哚美辛外，所有非甾体抗炎药均显著降低组胺刺激的胃酸分泌。非甾体抗炎药对胃蛋白酶原分泌没有影响。雷尼替丁预处理（腹腔注射25毫克/千克）使所有治疗组的基础胃酸和胃蛋白酶原分泌分别显著降低>85%和>40%，水杨酸盐、阿司匹林和吲哚美辛诱导的溃疡也分别被抑制了90%、60%和60%。在基础分泌条件下，非甾体抗炎药对前列腺素E2生成的抑制作用似乎与溃疡形成的程度相关。我们的数据支持这样一个概念，即除了抑制前列腺素E2合成外，胃酸在非甾体抗炎药诱导的胃病发病机制中也起重要作用。
