目的: 通过对已知阳性剂奥美拉唑镁盐的检测,建立并优化4种胃黏膜损伤动物模型,为药品、保健食品等技术规范的修订提供依据。方法: 设奥美拉唑镁盐2.5、5.0、10.0 mg·kg^-1组和去离子水模型对照组,对小鼠水浸应激性胃黏膜损伤、大鼠无水乙醇诱发胃黏膜损伤、大鼠幽门结扎胃黏膜损伤、大鼠冰醋酸浸渍胃黏膜损伤等4种急、慢性动物模型进行定量细化研究。结果: 在建立并优化后的4种动物胃黏膜损伤模型中,模型对照组显示胃黏膜损伤部位清晰易辨,方便计数损伤个数或测量损伤面积;奥美拉唑镁盐各剂量组对小鼠和大鼠的胃黏膜损伤有明显的保护作用,当剂量≥2.5 mg·kg^-1,前3种模型的黏膜损伤面积抑制率分别达到63.5%、50.0%及47.5%以上,第4种模型的溃疡面积抑制率≥28.8%;当剂量≥5.0 mg·kg^-1,第4种模型的溃疡体积抑制率≥45.4%;统计学分析均具有显著性差异（P<0.05）。结论: 造模期间应严格执行大、小鼠禁食时间和禁食方式,保证胃排空。用1%甲醛溶液定量对胃内充盈固定,将皱缩的胃黏膜充分伸展,便于准确观察、计数黏膜损伤数量、测量黏膜损伤面积或溃疡面积,避免误判,其精确度有明显提高。优化后的方法能够更好地应用于评价药品或保健食品对胃黏膜损伤的保护作用,同时提供了阳性剂奥美拉唑镁盐的剂量选择依据。

Objective：To establish and optimize four animal models of gastric mucosal injury through the detection of the known positive agent, omeprazole magnesium salt, providing a basis for the revision of technical standards for drugs and health foods, etc. Methods：The groups with omeprazole magnesium salt at doses of 2.5, 5.0 and 10.0 mg·kg^-1 and deionized water model control group were set up to quantitatively refine four acute and chronic animal models, including gastric mucosal injury caused by water immersion stress in mice, gastric mucosal injury induced by absolute ethanol in rats, gastric mucosal injury caused by pyloric ligation in rats, and gastric mucosal injury impregnated with glacial acetic acid in rats. Results：The model control group exhibited clear and distinguishable gastric mucosal injury sites in the four optimized animal models, facilitating accurate counting of injury numbers or measurement of lesion areas. Omeprazole magnesium salt at all tested doses demonstrated significant protective effects on gastric mucosal injury in both mice and rats. When the dose was ≥2.5 mg·kg^-1, the inhibition rates of mucosal injury area in the first three models reached more than 63.5%, 50.0% and 47.5% , respectively and the inhibition rate of ulcer area ≥28.8% in the fourth model. When the dose was ≥5.0 mg·kg^-1, the inhibition rate of ulcer volume was ≥45.4% in the fourth model. There were significant differences in statistical analysis (P<0.05). Conclusion：During the modeling period, the fasting time and fasting method of rats and mice should be strictly implemented to ensure gastric emptying. Quantitative gastric filling and fixation with 1% formaldehyde solution effectively stretch the wrinkled gastric mucosa, enabling accurate observation, ulcer counting, and measurement of ulcer injury areas, thus minimizing misjudgment and significantly improving precision. The optimized method can be better applied to evaluate the protective effect of drugs or health foods on gastric mucosal injury. At the same time, it provides a basis for the dose selection of omeprazole magnesium salt.