Arai I, Hirose H, Muramatsu M, Okuyama S, Aihara H
Jpn J Pharmacol. 1985 Jan;37(1):91-9. doi: 10.1254/jjp.37.91.
Effects of several non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin (ASA), indomethacin (IM), flurbiprofen (FP), ibuprofen (IP), phenylbutazone (PBZ) and flufenamic acid (FA) were studied on the gastric ulceration and gastric acid secretion induced by restraint and water-immersion stress (RWIS) or various secretagogues in rats. These drugs significantly increased ulcer formation. IM (1, 3 and 10 mg/kg, s.c.) reduced gastric mucosal prostaglandin (PG) content dose-dependently. There was an appreciable correlation between this decrease in the PG content of gastric tissue and associated ulceration. The gastric acid secretion induced by the peripheral secretagogues, methacholine, gastrin and histamine, was not significantly influenced by IM pretreatment. In contrast, the gastric acid secretion induced by the vagal mediated secretagogues, insulin, 2-deoxy-D-glucose (2-D-G) and RWIS, was markedly increased by IM pretreatment. These effects were not observed in vagotomized rats. By intracerebroventricular (i.c.v.) injection of IM, no influence was observed on the gastric acid secretion and ulcer formation induced by 2-D-G or RWIS. These results suggest that acidic NSAIDs potentiate the gastric acid output induced by stimulation of vagus nerve activity, and prostaglandins (PGs) may influence gastric acid output by regulating vagus nerve activity.
研究了几种非甾体抗炎药（NSAIDs），如阿司匹林（ASA）、吲哚美辛（IM）、氟比洛芬（FP）、布洛芬（IP）、保泰松（PBZ）和氟芬那酸（FA）对束缚和水浸应激（RWIS）或各种促分泌剂诱导的大鼠胃溃疡和胃酸分泌的影响。这些药物显著增加溃疡形成。IM（1、3和10mg/kg，皮下注射）剂量依赖性地降低胃黏膜前列腺素（PG）含量。胃组织中PG含量的这种降低与相关溃疡形成之间存在明显的相关性。外周促分泌剂乙酰甲胆碱、胃泌素和组胺诱导的胃酸分泌不受IM预处理的显著影响。相反，迷走神经介导的促分泌剂胰岛素、2-脱氧-D-葡萄糖（2-D-G）和RWIS诱导的胃酸分泌在IM预处理后显著增加。在迷走神经切断的大鼠中未观察到这些效应。通过脑室内（i.c.v.）注射IM，未观察到对2-D-G或RWIS诱导的胃酸分泌和溃疡形成的影响。这些结果表明，酸性NSAIDs增强了迷走神经活动刺激诱导的胃酸分泌，前列腺素（PGs）可能通过调节迷走神经活动影响胃酸分泌。
