雷贝拉唑对NSAIDs相关小肠损伤大鼠紧密连接蛋白Occludin表达的影响及其机制  

The effects and mechanism of rabeprazole on tight junction protein occludin expression in rats with non-steroid anti-inflammatory drugs(NSAIDs) induced small intestinal injury

作　　者：高欣[1] 张振玉[1] 吴海露[1] 胡可伟[1] 姜宗丹[1] 杨小兵[2] 王劲松[2] 

机构地区：[1]南京医科大学附属南京第一医院消化科,江苏南京210006 [2]南京医科大学附属南京第一医院病理科,江苏南京210006

出　　处：《胃肠病学和肝病学杂志》2012年第8期771-774,共4页Chinese Journal of Gastroenterology and Hepatology

摘　　要：目的探讨雷贝拉唑对非甾体类抗炎药(NSAIDs)相关性小肠损伤大鼠紧密连接蛋白Occludin表达的影响及可能的机制。方法将36只SD大鼠随机平均分为阴性对照组、双氯酚酸损伤组和雷贝拉唑处理组。采用双氯酚酸7.5 mg/(kg.d)灌胃,连续4 d,制造大鼠NSAIDs相关性小肠损伤模型;而雷贝拉唑处理组在每次造模前0.5 h予以15 mg/(kg.d)雷贝拉唑灌胃处理,连续4 d。处死大鼠进行大体及病理观察小肠损伤情况,采用免疫组织化学和Western blot方法检测小肠组织中Occludin和磷酸化ERK(p-ERK)蛋白表达水平的变化。结果雷贝拉唑处理组大鼠大体和病理损伤均低于损伤组(P<0.05)。Occludin蛋白在损伤组中表达较对照组明显下降(P<0.05),而在雷贝拉唑处理组中的表达较损伤组上升(P<0.05);与阴性对照组相比,p-ERK蛋白在损伤组中表达上升(P<0.05),在雷贝拉唑处理组中的表达较损伤组下降(P<0.05)。结论雷贝拉唑对大鼠NSAIDs相关性损伤有保护作用,其机制可能是通过MAPK中的ERK途径,增加小肠上皮组织中Occludin蛋白表达,从而增强肠黏膜屏障功能。Objective To explore the effects and mechanism of raheprazole on tight junction protein occludin expres- sion in rats with non-steroid anti-inflammatory drugs （NSAIDs） induced small intestinal injury. Methods 36 SD rats were randomly and equally divided into control group, injury group amt rabeprazole treated group. Except control group, rats of other two groups were garaged with diclofenac 7.5 rag/（kg ~ d） , once daily to make NSAIDs related small intes- tinal injury model. The treated group was gavaged with rabeprazola 15 mg/（kg ~ d） once daily 0.5 h before the admin- istration of diclofenac. Continuous administration for four days and then executed, small intestinal tissues were taken and observed for gross and pathology changes. Immunohistochemistry and Western blot were used to detect the distribution and expression of intestinal epithelial tight junction protein occludin. The expression of phosphorylation-ERK （p-ERK） was determined by Western blot. Results Compared with injury group, the gross and tissue injury scores of rabeprazole treated group significantly decreased （P 〈 0.05）. The expression of occludin in injury group was decreased significantly compared with normal group （ P 〈 0.05 ）, however, rabeprazole treated group decreased lightly （P 〈 0.05 ）. Significant activation of ERK were more obvious in injury group than that in normal group （P 〈 0.05） , but pretreatment with rabe- prazole could inhibit the activation of ERK （P 〈 0.05）. Conclusion Rabeprazole has a protective effect on NSAIDs in- duced small intestinal injury in rats, probably increasing the expression of tight junction protein occludin by acting ERK signaling pathways.

关 键 词：雷贝拉唑 NSAIDs相关性小肠损伤 OCCLUDIN蛋白 MAPK/ERK信号通路 

分 类 号：R574[医药卫生—消化系统]