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

目的：内源性和外源性洋地黄素（PGs）已被证明有助于减少随后给予刺激物引起的胃损伤。本研究的目的是阐明预处理诱导的环氧合酶-2（考克斯-2）蛋白是否参与预防随后的乙醇引起的小鼠胃损伤。研究方法：用酸化乙醇或生理盐水预处理小鼠，然后每8小时在胃中用化学方法测定考克斯-2蛋白表达。在酸化乙醇预处理后24小时给予小鼠95%乙醇，并在肉眼和组织学上评价胃粘膜损伤。还检查了NS-398或吲哚美辛对95%乙醇引起的损伤的作用。结果如下：酸化乙醇预处理可诱导胃粘膜固有层巨噬细胞考克斯-2蛋白表达，24 h后达高峰。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差异。然而，NS-398加重乙醇引起的损害，只有在小鼠预处理酸化乙醇，而吲哚美辛加重损伤的组织学评价与预处理无关。结论：除考克斯-1外，预处理诱导的考克斯-2似乎通过最小化由随后的刺激物引起的损害而参与防御机制.

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.