瑞巴派特对大鼠非甾体类抗炎药相关性小肠损伤的保护作用及机制  

Protective effect of rabamipide on non-steroid anti-inflammatory drug induced enteropathy in rats

作　　者：刘晨晨[1] 段兆涛[1] 袁芳岑[1] 姜宗丹[1] 汪志兵[1] 杨小兵[2] 王劲松[2] 张振玉[1] 

机构地区：[1]南京医科大学附属南京医院(南京市第一医院)消化科,江苏省南京市210006 [2]南京医科大学附属南京医院(南京市第一医院)病理科,江苏省南京市210006

出　　处：《世界华人消化杂志》2015年第24期3838-3845,共8页World Chinese Journal of Digestology

基　　金：南京市医学科技发展基金资助项目;No.YKK13103~~

摘　　要：目的:探讨瑞巴派特对大鼠非甾体类抗炎药(non-steroid anti-inflammatory drugs,NSAIDs)相关性小肠损伤的保护作用及可能的机制.方法:将30只健康♂SD大鼠随机分为阴性对照组、双氯芬酸损伤组、瑞巴派特保护组,每组10只.通过应用双氯芬酸7.5 mg/(kg·d)灌胃,1次/d、连续4 d的方法制作大鼠NSAIDs相关性小肠损伤模型.瑞巴派特保护组在每次造模前1 h用100 mg/(kg·d)瑞巴派特对大鼠进行灌胃预处理,连续4 d.阴性对照组应用等量的生理盐水灌胃,实验第4天,处死所有大鼠,对其小肠损伤情况进行大体及病理观察并评分,采用免疫组织化学方法检测小肠黏膜中Occludin蛋白的表达和分布,采用Western blot方法检测小肠组织中Occludin蛋白、ERK、p38和磷酸化ERK(p-ERK)、磷酸化p38(p-p38)蛋白表达水平.结果:损伤组大鼠小肠大体和病理损伤评分均高于对照组(P<0.05),瑞巴派特组大鼠小肠大体和病理损伤评分均低于损伤组(P<0.05);Occludin蛋白在损伤组中表达水平较对照组明显降低(P<0.05),而在瑞巴派特处理组中的表达水平较损伤组增高(P<0.05);与对照组相比,损伤组中p-ERK蛋白和p-p38表达水平增高(P<0.05),而瑞巴派特处理中的表达水平较损伤组降低(P<0.05).结论:瑞巴派特对大鼠NSAIDs相关性小肠损伤有一定的保护作用,其机制可能通过抑制丝裂原活化蛋白激酶(mitogen-activated protein kinases,MAPKs)信号通路中ERK和p38蛋白的磷酸化,上调小肠黏膜中紧密连接Occludin蛋白表达,从而改善小肠黏膜屏障功能.AIM： To investigate the effect of rabamipide on non-steroid anti-inflammatory drug（NSAID）induced enteropathy in rats and the possible mechanism. METHODS： Thirty male Sprague-Dawley rats were randomized into three groups： a control group, a diclofenac induced injury group, and a rabamipide pretreatment group. Intestinal injury was induced in rats of the diclofenac induced injury group and rabamipide pretreatment group by intragastric administration of diclofenac（7.5 mg/kg） once per day for continuous 4 d. The rabamipide pretreatment group was pretreated with rabamipide 100 mg/（kg·d） orally once daily 1 h before the administration of diclofenac.The control group received 0.9% Na Cl by gavage during the same period. All the rats were sacrificed on the 4th day. Small intestinal injuries were assessed for histopathological damage and macroscopic injury and recorded as corresponding scores. Immunohistochemistry and Western blot were used to detect the distribution and expression of intestinal epithelial tight junction protein occludin. The expression of ERK, p38, phosphorylated ERK（p-ERK） and phosphorylated p38（p-p38） was determined by Western blot. RESULTS： Compared with the control group,histopathological and macroscopic scores of intestinal damage were significantly increasedin the diclofenac induced injury group（P 〈0.05）. Intestinal damage scores in the rabamipide pretreatment group were signif icantly decreased compared with those in the diclofenac induced injury group（P 〈0.05）. Compared with the control group, expression of occludin in the diclofenac induced injury group was decreased significantly（P 0.05）, while that in the rabamipide pretreatment group increased significantly compared with the diclofenac induced injury group（P 〈0.05）. Significant activation of ERK and p38 was seen in the diclofenac induced injury group compared with the control group（P〈 0.05）, and pretreatment with rabamipide significantly inhibited the activation of ERK and p38 compared

关 键 词：瑞巴派特 非甾体类抗炎药相关性小肠损伤 OCCLUDIN MAPKS信号通路 

分 类 号：R965[医药卫生—药理学]