NSAIDs相关性大鼠小肠黏膜PGE_2、COX的表达及药物保护机制  

Expression of PGE_2 and COX in intestinal injury induced with non-steroidal anti-inflammatory drugs in rats: Implications for protective effects of drugs

作　　者：丁瑞峰[1] 郭元虎[1] 韩文鹏 王爱鱼[1] 田晓娟[1] 

机构地区：[1]包头医学院第一附属医院消化科,内蒙古自治区包头市014010 [2]山东青岛市城阳人民医院消化科,山东省青岛市266109

出　　处：《世界华人消化杂志》2013年第30期3241-3246,共6页World Chinese Journal of Digestology

基　　金：内蒙古自治区自然科学基金资助项目;No.2011MS1173

摘　　要：目的:双氯芬酸灌胃建立非甾体类抗炎药(non-steroidal anti-inflammatory drug,NSAID)相关性大鼠小肠黏膜损伤模型,研究大鼠小肠黏膜前列腺素E2(prostaglandin E2,PGE2)、环氧合酶-1(cyclooxygenase 1,COX-1)和环氧合酶-2(COX-2)的表达及药物的作用机制.方法:32只♂Wistar大鼠随机分为空白组、实验对照组、药物干预组(荆花胃康胶丸组、埃索美拉唑组).实验对照组和药物干预组给予双氯芬酸,药物干预组提前1 d分别给予荆花胃康胶丸和埃索美拉唑.空白组给予生理盐水.处死大鼠后显微镜下观察大鼠小肠损伤情况,取小肠组织ELISA法检测小肠组织PGE2含量,Western blot法检测小肠组织COX-1、COX-2蛋白表达.结果:与空白对照组相比,实验对照组大鼠小肠大体评分(4.63±0.52 vs 0.00±0.00)明显增高,差异有统计学意义(P<0.05);与实验对照组相比,荆花胃康组、埃索美拉唑组大鼠小肠大体评分(1.88±0.99,2.75±1.28)明显降低,差异有统计学意义(P<0.05).与空白组相比,实验对照组大鼠小肠黏膜PGE2(19.32ng/L±8.22 ng/L vs 36.64 ng/L±3.27 ng/L)明显降低,差异有统计学意义(P<0.05);与实验对照组相比,荆花胃康组、埃索美拉唑组大鼠小肠PGE2(29.51 ng/L±7.61 ng/L;29.20ng/L±7.51 ng/L)明显增加,差异有统计学意义(P<0.05).与空白组相比,实验对照组大鼠小肠黏膜COX-1(0.47±0.32 vs 0.78±0.39)明显降低,差异有统计学意义(P<0.05);与实验对照组相比,荆花胃康组、埃索美拉唑组大鼠小肠COX-1(1.29±0.63,1.53±1.00)明显增加,差异有统计学意义(P<0.05).与空白组相比,实验对照组大鼠小肠黏膜COX-2(1.00±0.72 vs 0.00±0.00)明显增加,差异有统计学意义(P<0.05);与实验对照组相比,荆花胃康组大鼠小肠黏膜COX-2(6.86±9.81)明显增加,差异有统计学意义(P<0.05);与实验对照组相比,埃索美拉唑组大鼠小肠黏膜COX-2(2.59±2.87)增加,差异无统计学意义(P>0.05).结论:双氯芬酸可以引起典型的NSAIAIM： To investigate the expression of prostaglandin E2 （PGE2）, cyclooxygenase 1 （COX-1） and cyclooxygenase 2 （COX-2） in diclofenac sodium-induced intestinal injury in rats and to analyze their implications for protective effects of drugs. METHODS： Thirty-two male Wistar rats were randomly and equally divided into four groups： a normal control group （given normal saline）, a model control group （given diclofenac sodium）, and two treatment groups （given Jinghua Weikang Jiaowan and esomeprazole, respectively）. Except for the normal control group, intestinal injury was induced with diclofenac sodium in the other groups. Jinghua Weikang Jiaowan and esomeprazole were administered in the two treatment groups from the day before diclofenac sodium was given. Intestinal injury was observed by microscopy. The content of PGE2 in the small intestine tissues was tested by ELISA. The expression of COX-1 and COX-2 proteins was detected by Western blot. RESULTS： Compared to the normal control group, the morphological score increased significantly in the model control group （4.63 ± 0.52 vs 0.00 ± 0.00, P 〈 0.05）; however, the morphological score was significantly lower in the two treatment groups than in the model control group （1.88 ± 0.99, 2.75 ± 1.28, both P 〈 0.05）. Compared to the normal control group, the content of PGE2 was significantly lower in the model control group （19.32 ng/L ± 8.22 ng/L vs 36.64 ng/L ± 3.27 ng/L, P 〈 0.05）; however, the content of PGE2 increased significantly in the two treatment group increased significantly compared to the model control group （29.51 ng/L ± 7.61 ng/L, 29.20 ng/L ± 7.51 ng/L, both P 〈 0.05）. The expression level of COX-1 was significantly lower in the model control group than in the normal control group （0.47 ± 0.32 vs 0.78 ± 0.39, P 〈 0.05）; however, the expression of COX-1 increased significantly in the treatment group compared to the model control group （1.29 ± 0.63, 1.53 ± 1.00, both P 〈 0.05）. Com

关 键 词：小肠损伤 非甾体类消炎药 前列腺素E2 环氧合酶 

分 类 号：R965[医药卫生—药理学]