摘要
背景:研究显示非甾体抗炎药(NSAIDs)不仅可引起胃十二指肠黏膜损伤,还可引起小肠黏膜损伤。目的:探讨NSAIDs引起小肠黏膜损伤的发病机制及其病理生理变化。方法:50只大鼠随机分为空白对照组和四组模型组,以不同NSAID灌胃14d。另20只大鼠先分别行胆管结扎和假手术,再予吲哚美辛灌胃。观察各组大鼠一般情况和小肠黏膜大体、组织病理学改变,测定小肠组织髓过氧化物酶(MPO)、丙二醛(MDA)、超氧化物歧化酶(SOD)、一氧化氮(NO)含量。结果:四种NSAID均能造成大鼠小肠黏膜损伤,吲哚美辛、布洛芬和塞来昔布组累计损伤深度和面积显著高于空白对照组(P<0.05),其中以吲哚美辛组损伤最重,阿司匹林组则与空白对照组无明显差异。各模型组小肠组织MPO含量均显著高于空白对照组,SOD活性则显著低于空白对照组(P<0.05),MDA和NO含量均呈上升趋势,但分别仅吲哚美辛组和布洛芬组与空白对照组相比有显著差异(P<0.05)。假手术组小肠黏膜损伤显著重于空白对照组(P<0.05),胆管结扎组与空白对照组相比无明显差异。结论:NSAIDs可通过炎症反应、氧自由基损伤、NO过度产生以及药物的肝肠循环损害小肠上皮屏障,破坏小肠结构的完整性。
Background： It has been demonstrated that non-steroidal anti-inflammatory drugs （NSAIDs） can cause damage not only to gastroduodenal mucosa but also to small intestinal mucosa. Aims： To investigate the mechanism of small intestinal mucosal injury induced by NSAIDs and its pathophysiologie changes. Methods： Fifty rats were randomly allocated into blank control group and four model groups in which intragastric infusion of different NSAID was given for 14 days. Other 20 rats were taken for ligation of bile duct and sham operation, respectively, and then were infused with indomethaein intragastrieally. The general conditions, macroscopic and microscopic changes of small intestinal mucosa, and concentrations of myeloperoxidase （MPO）, malondialdehyde （MDA）, superoxide dismutase （SOD） and nitric oxide （NO） in small intestinal tissues were examined. Results： Aspirin, indomethacin, ibuprofen and celecoxib all could cause damage to small intestinal mucosa, the accumulated surface area and depth of lesions were significantly greater than those in blank controls except aspirin （P〈0.05）; the damage in indomethacin group was the most severe. All these drugs significantly increased the concentration of MPO and decreased the activity of SOD in small intestinal tissues as compared with those of blank controls （P〈0.05）. Concentrations of MDA and NO had a tendency to increase, but statistically significant differences were seen only in indomethacin group and ibuprofen group, respectively （P〈0.05）. Small intestinal mucosal injury of sham operation group, but not bile duct ligation group, was more severe than that of blank controls （P〈0.05）. Conclusions： Inflammation, oxygen free radicals injury and overproduction of NO induced by NSAIDs and the hepatoenteral circulation of NSAIDs may impair the epithelial barrier of small intestine, and destroy the structural integrity of small intestine.
出处
《胃肠病学》
2008年第9期536-539,共4页
Chinese Journal of Gastroenterology
关键词
消炎药
非甾类
小肠/损伤
自由基
肝肠循环
Anti-Inflammatory Agents, Non-Steroidal
Intestine, Small/injuries
Free Radicals
Hepatoenteral Circulation
