呱氨托美汀的抗炎作用及对胃肠黏膜的影响

The effects of amtolmetin guacyl on acute inflammation and gastroduodenal mucosa

目的研究呱氨托美汀(AMG)对急性炎症模型的抗炎作用以及对胃肠黏膜的影响及其机制。方法采用二甲苯诱导的小鼠耳肿胀及棉球诱导的大鼠肉芽肿模型,观察AMG对炎症反应的抑制作用,同时进行胃及十二指肠黏膜损伤评分,分光光度法检测胃组织MDA含量,Griess试剂法测定大鼠血浆及胃组织NO2-含量。结果AMG与其代谢产物托美汀(TOL)均能显著抑制二甲苯诱导的小鼠耳肿胀和棉球诱导的大鼠肉芽肿(P<0.05)。AMG组胃肠黏膜损伤评分与溶剂对照组比较,差异无显著性(P>0.05),而TOL组损伤评分显著性升高(P<0.05)。AMG明显升高胃组织匀浆NO2-水平,并明显减少MDA含量(P<0.05),而TOL对NO2-水平无明显影响且显著升高胃组织匀浆MDA含量(P<0.05)。结论AMG的抗炎作用与其代谢产物TOL相当,但具有较强的改善胃肠黏膜损伤的效应,其机制可能与其升高胃组织NO2-水平及减少MDA含量有关。

Objective To study the effects of amtolmetin guacyl（AMG） on acute inflammation and gastroduodenal mucosa. Methods Xylene induced ear swelling in mice and cotton pellet induced granuloma in rats were developed, the anti-inflammatory activities of AMG were observed, the score of gastroduodenal mucosal damage were evaluated, the levels of MDA in gastric mucosal homogenates were assayed by ultraviolet spectrophotometer method, the contents of NO2^- in plasma and gastric mucosal homogenates were measured by Griess reagent. Results AMG and its metabolite tolmetin（TOL） significantly inhibited the ear edema induced by xylene in mice and reduce the weight of granuloma induced by cotton pellet respectively （ P 〈 0.05 ）. AMG did not induce any appreciable gastroduodenal mucosal damage, but TOL administered at equimolar significantly produced gastric damage （P 〈 0.05 ）, AMG significantly increased the contents of NO2^- in gastric mucosal homogenates（P 〈0.05）. Furthermore,AMG significantly decreased the contents of MDA in gastric mucosal homogenates （ P 〈 0.05 ）, but TOL obviously increased the contents of MDA in gastric mucosal homogenates （P 〈 0.05 ）, and had no effect on the contents of NO2^- Conclusion The antiinflammatory activity of AMG is similar to TOL, but it shows strong gastroprotective effect, which may be relative to NO2^- pathways and MDA.