analysis of cytoprotection by COX-2 induced in gastric mucosa : influence by selective COX-2 inhibitors

目的：内源性和外源性前列腺素（pg）已被证明有助于减轻随后给予的刺激引起的胃损伤。本研究的目的是阐明预处理诱导的环氧合酶-2 （COX-2）蛋白是否参与了小鼠后续乙醇性胃损伤的预防。方法：小鼠经酸化乙醇或生理盐水预处理，每8 h免疫组化检测胃内COX-2蛋白表达。酸化乙醇预处理24小时后给予95%乙醇，观察胃粘膜损伤的宏观和组织学变化。研究了NS-398或吲哚美辛对95%乙醇损伤的影响。结果：酸化乙醇预处理诱导胃粘膜固有层巨噬细胞COX-2蛋白表达，预处理后24 h达到峰值。95%乙醇引起胃粘膜损伤。酸化乙醇和生理盐水预处理小鼠的损伤程度无显著差异。然而，NS-398只在酸化乙醇预处理的小鼠中加重了乙醇引起的损伤，而吲哚美辛加重了组织学上评估的损伤，与预处理无关。结论：预处理诱导的COX-2和COX-1似乎通过减少后续刺激引起的损伤参与了防御机制。

Purpose : Endogenous and exogenous prostaglandins (PGs) have been shown to contribute to reduce gastric injury caused by irritants given subsequently. The aim of the study is to clarify whether cyclooxygenase-2 (COX-2) protein induced by pretreatment is involved in prevention of subsequent ethanol-caused gastric injury in mice. Methods : Mice were pretreated with acidified ethanol or saline and then COX-2 protein expression was immunohistochemically determined at every 8 hours in the stomachs. Mice were administered 95 % ethanol 24 hours after acidified ethanol pretreatment and gastric mucosal damages were evaluated macroscopically and histologically. The effects of NS-398 or indomethacin on 95 % ethanol-caused damage were also examined. Results : Acidified ethanol pretreatment induced COX-2 protein expression in lamina propria macrophages of the gastric mucosa with its peak level 24 hours after the pretreatment. 95 % ethanol caused gastric mucosal damages. The degree of the damages was not different between mice pretreated with acidified ethanol and saline. However, NS-398 aggravated ethanol-caused damages only in mice pretreated with acidified ethanol, while indomethacin aggravated the damages evaluated histologically Irrespective of the pretreatment. Conclusions : The pretreatment- induced COX-2 in addition to COX-1 seems to be involved in the defense mechanism through minimizing damages caused by a subsequent irritant.