质子泵抑制剂对NSAIDs相关小肠损伤大鼠HO-1表达的影响  

Effects of Proton Pump Inhibitors on HO-1 Expression in Rats with NSAIDs-related Small Intestinal Injury

作　　者：陈汉卿[1] 吕宾[1] 陈鸣艳[1] 张烁[1] 

机构地区：[1]浙江中医药大学附属第一医院消化科,310006

出　　处：《胃肠病学》2011年第7期390-394,共5页Chinese Journal of Gastroenterology

摘　　要：背景:长期使用非甾体消炎药(NSAIDs)可引起小肠黏膜炎症性病变。质子泵抑制剂(PPI)除抑酸外还具有抗炎和抗氧化作用,并可上调胃黏膜血红素加氧酶-1(HO-1)的表达。目的:探讨不同PPI对NSAIDs相关小肠损伤大鼠HO-1表达的影响。方法:将Sprague-IDawley大鼠随机分为空白对照组、模型组和4组PPI治疗组。给予大鼠双氯芬酸钠7.5 mg/kg灌胃,以制备NSAlDs相关小肠损伤大鼠模型。各PPI治疗组分别以奥美拉唑30 mg/kg、埃索美拉唑30mg/kg、雷贝拉唑15 mg/kg、兰索拉唑45 mg/kg灌胃治疗。实验第6 d,处死所有大鼠,观察小肠组织大体和病理变化,以实时荧光定量PCR和蛋白质印迹法分别检测小肠组织HO-1 mRNA和蛋白表达。结果:埃索美拉唑、雷贝拉唑、兰索拉唑治疗组大体和病理评分均显著低于模型组(P<0.05),雷贝拉唑、兰索拉唑治疗组小肠组织HO-1 mRNA和蛋白表达较模型组明显升高(P<0.05),而奥美拉唑治疗组上述指标与模型组相比均无明显差异。结论:不同PPI对NSAIDs相关小肠损伤的保护作用不同,其机制可能与上调HO-1 mRNA和蛋白表达有关,但奥美拉唑无明显保护作用。Background： Long-term use of non-steroid anti-inflammatory drugs （NSAIDs） can cause inflammation of small intestinal mucosa. Besides inhibiting acid secretion, proton pump inhibitors （PPI） also have anti-inflammatory and antioxidant effects. Moreover, PPI can up-regulate the expression of gastric mucosal heme oxygenase-1 （HO-1）. Aims： To study the effects of PPI on expression of HO-1 in rats with NSAIDs-related small intestinal injury. Methods： Sprague- Dawley rats were randomly divided into six groups： blank control group, model group and 4 PPI treatment groups. Diclofenae sodium 7.5 mg/kg was given intragastrically to rats to establish the model of NSAIDs-related small intestinal injury. In the 4 PPI treatment groups, omeprazole 30 mg/kg, esomeprazole 30 mg/kg, rabeprazole 15 mg/kg and lansoprazole 45 mg/kg were given to the rats, respectively. On the 6th day, all the rats were sacrificed. The gross and pathological changes of small intestinal tissue were observed. Expressions of HO-1 mRNA and protein were determined by real time fluorescent quantitative PCR and Western blotting, respectively. Results： Gross and pathological score in esomeprazole, rabeprazole and lansoprazole treatment groups were significantly lower than those in model group （P〈0.05）. The expressions of HO-1 mRNA and protein in small intestinal tissue in rabeprazole and lansoprazole treatment groups were significantly higher than those in model group （P〈0.05）. However, no significant differences of above-mentioned indices were seen between omeprazole treatment group and model group. Conclusions： Different PPI have different protective effects on rats with NSAIDs-related small intestinal injury. The mechanism of protection by PPI may be related to the up-regulation of expressions of HO-1 mRNA and protein. Omeprazole has no obvious protective effect.

关 键 词：质子泵抑制剂 消炎药 非甾类 小肠 血红素加氧酶-1 

分 类 号：R96[医药卫生—药理学]