Tanaka H, Takeuchi K, Okabe S
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Jpn J Pharmacol. 1989 Oct;51(2):291-7. doi: 10.1254/jjp.51.291.
A single s.c. administration of histamine dose-dependently (5-20 mg/kg) induced villous damage of the proximal duodenum in 24-hr fasting rats. Time course studies indicate that histamine (20 mg/kg) induced severe exfoliation of the epithelial cells at the villous tips of the duodenal mucosa 0.5 hr after administration. The damage, however, tended to heal with time, and recovery was nearly complete 8 hr later. This villous damage was significantly inhibited by pretreatment with sodium bicarbonate given orally or cimetidine, omeprazole and NC-1300 given subcutaneously. Histamine (20 mg/kg) significantly stimulated gastric acid secretion and lowered the intraduodenal pH for 1 hr. Gastric content was significantly greater than that in the control group for 1 hr after histamine administration, probably due to stimulated gastric secretion and delayed emptying. We conclude that a single administration of histamine induces microscopical duodenal damage by stimulation of gastric acid secretion, but the damage heals with time, probably as a result of the short periods of acid stimulation and delayed emptying.
对禁食24小时的大鼠单次皮下注射组胺（剂量为5 - 20毫克/千克）会剂量依赖性地诱导十二指肠近端绒毛损伤。时间进程研究表明，组胺（20毫克/千克）在给药后0.5小时会诱导十二指肠黏膜绒毛尖端的上皮细胞严重脱落。然而，这种损伤会随时间趋于愈合，8小时后几乎完全恢复。口服碳酸氢钠或皮下注射西咪替丁、奥美拉唑和NC - 1300预处理可显著抑制这种绒毛损伤。组胺（20毫克/千克）可显著刺激胃酸分泌，并使十二指肠内pH值降低1小时。组胺给药后1小时，胃内容物显著多于对照组，这可能是由于胃酸分泌受刺激和排空延迟所致。我们得出结论，单次注射组胺通过刺激胃酸分泌诱导十二指肠微观损伤，但这种损伤会随时间愈合，可能是由于酸刺激时间短和排空延迟的结果。
