奥美拉唑与雷贝拉唑对大鼠肠道P-糖蛋白作用比较  

Comparative study of the effects of omeprazole and rabeprazole on intestinal P-glycoprotein in rats

作　　者：方海明[1] 王佳佳[2] 章礼久[1] 许建明[3] 梅俏[3] 陆春霞[1] 

机构地区：[1]安徽医科大学第二附属医院消化内科,安徽合肥230601 [2]安徽医科大学药理教研室,安徽合肥230601 [3]安徽医科大学第一附属医院消化内科,安徽合肥230601

出　　处：《中国医院药学杂志》2013年第1期7-11,共5页Chinese Journal of Hospital Pharmacy

基　　金：安徽省高校优秀青年人才基金重点项目(NO.2010SQRL075ZD);安徽省省教育厅自然科学基金项目(NO.KJ2010B390;KJ2011Z191)

摘　　要：目的:探讨连续服用奥美拉唑和雷贝拉唑对大鼠肠道P-糖蛋白(P-gp)功能及蛋白表达的影响。方法:30只大鼠随机分为5组,每组6只,即奥美拉唑组、雷贝拉唑组、地塞米松组、维拉帕米组及正常对照组,分别灌胃给药,对照组给予等剂量生理盐水,连续7 d,第8天处死动物,取空肠、回肠、结肠制成外翻肠囊,采用荧光分光光度计测定囊外液(AP侧)罗丹明123的浓度,计算罗丹明123转运速率。应用免疫组化方法的测定不同肠段P-gp蛋白表达变化。结果:处理90min,奥美拉唑组空肠、回肠及结肠AP侧累积浓度分别为(2.7±0.5)、(1.95±0.21)ng.mL-1和(0.78±0.24)ng.mL-1,显著低于对照组(P<0.05),抑制程度依次为空肠>回肠>结肠,BL→AP转运速率分别为(0.05±0.01)、(0.04±0.02)ng.mL-1.cm-1和(0.01±0.01)ng.mL-1.cm-1;各肠段P-gp蛋白表达水平分别为(0.35±0.02)、(0.45±0.05)和(0.43±0.07),显著低于对照组(P<0.05),抑制程度依次为空场<回肠<结肠。雷贝拉唑组空肠、回肠及结肠BL→AP转运速率分别为(0.11±0.05)、(0.06±0.02)ng.mL-1.cm-1和(0.02±0.01)ng.mL-1.cm-1,各肠段P-gp蛋白表达水平分别为(0.42±0.05)、(0.47±0.06)和(0.52±0.07),与对照组比较,均无统计学意义(P>0.05)。结论:连续口服奥美拉唑能显著抑制大鼠肠道黏膜P-gp功能和蛋白表达,而连续口服雷贝拉唑未见上述作用。OBJECTIVE To investigate the effects of consecutive administration of omeprazole or rabeprazole on the intestinal P-gp activity and protein expression in rats. METHODS 30 rats were divided into five groups randomly as omeprazle, rabeprazole, verapamil, dexamethasone and control group, respectively. Drugs were given to rats by intragastric administration once per day for 7 days. The control group was given the same dose of saline. On d8, rats were sacrificed, everted sac of jeju num, ileum and colon were prepared quickly concentration of rhodamine 123 at AP side were analyzed by fluorescence spectro photometer assays. Transport rates of rhodamine-123 were also caculated. Expressions of P-gp in jejunum, ileum and colon of rat were analyzed by immunohistoehemistry assays. RESULTS After 90 min, the accumulated concentration of rhodamine-123 at AP side of the everted jejunum, ileum and colon segments in the omeprazole group was （2. 7 ± 0. 5）, （ 1.95 ± 0. 21 ） ng.mL -1 and （0. 78 ± 0. 24） ng.mL-1 respectively. Transport rate of rhodamine-123 from BL to AP was （0. 05 ± 0. 01 ）, （0. 04 ± 0. 02）ng .mL-1 .min-1 and （0. 01 ± 0. 01）ng.mL-1 .min-1,respectively. Mean Pgp protein expression level on jejunum, ileum and colon was （0. 35 ± 0. 02）, （0. 45 ± 0. 05） and （0. 43 ± 0. 07） ,respectively. Compared with the control group, the accumulated concen tration and P-gp protein expression levels had significantly differences respectively （P〈0. 05）, while there were no differences between the transport rate. In rabeprazole group,, the accumulated concentration of rhodamine-123 at AP side the everted jeju num, ileum and colon segments was （4. 6 ± 1.2）, （2. 91 ± 0. 2）ng.mL-1 and （1.4 ±0.4） ng.mL-1, respectively. Transport rate was （0. 11 ± 0. 05）, （0. 06 ± 0. 02） ng .mL-1 .min-1 and （0. 02 ± 0. 01）ng .mL-1 .min-1, respectively. Mean P-gp protein expression level was （0. 42 ± 0.05）, （0. 47 ± 0. 06） and （0. 52 ± 0. 07）, respectively. CONCLUSI

关 键 词：奥美拉唑 雷贝拉唑 P-糖蛋白 外翻肠囊 免疫组化 罗丹明123 

分 类 号：R963[医药卫生—微生物与生化药学]