埃索美拉唑对人胃上皮细胞抗氧化损伤的保护作用及分子机制研究  

Protective Effect and Molecular Mechanism of Esomeprazole on Human Gastric Epithelial Cells Caused by Oxidative Injury

作　　者：胡杨[1] 吴清[1] 刘朝霞[1] 傅念[1] 阳学风[1] 

机构地区：[1]南华大学附属南华医院消化内科,湖南省衡阳市421000

出　　处：《中国全科医学》2014年第15期1731-1734,共4页Chinese General Practice

基　　金：衡阳市2012年科学技术发展项目(2012KJ18)

摘　　要：目的观察埃索美拉唑在氧化应激条件下对胃上皮细胞的保护作用,并探讨可能的分子机制。方法体外培养胃上皮细胞系AGC细胞,用不同浓度埃索美拉唑(0.1、0.5、1.0μg/ml)处理8 h,光泽精化学发光分析法检测其对活性氧(ROS)产生的影响,实时定量聚合酶链式反应法检测血红素氧合酶1(HO-1)和环氧化酶(COX)mRNA表达,Western blotting法检测HO-1蛋白表达水平,比色法测定HO-1酶活性。结果 AGS细胞与埃索美拉唑孵育8 h后,能显著抑制还原型烟酰胺腺嘌呤二核苷酸磷酸(NADPH)诱导的ROS产生。其中1.0μg/ml埃索美拉唑能使ROS产生量降低(73.3±3.5)%。实时定量聚合酶链式反应结果显示,0.5μg/ml埃索美拉唑处理后,HO-1mRNA增高8.2倍;1.0μg/ml埃索美拉唑处理后,HO-1 mRNA增高了38.4倍。不同浓度的埃索美拉唑刺激AGS细胞后,HO-1蛋白的表达量及HO-1酶活性随其浓度的递增而增高。埃索美拉唑处理后,AGS细胞内COX-1和COX-2 mRNA表达水平无变化。而AGS细胞首先经30μmol/L萘普生和罗非昔布分别作用后,对HO-1表达无影响。结论埃索美拉唑可能通过上调HO-1的表达而发挥对胃上皮细胞的抗氧化保护作用。Objective To observe the protective effect and molecular mechanism of Esomeprazole on human gastric epithelial cells under oxidative injury.Methods Human gastric epithelial cell line AGS was cultured in vitro and was incubated with different concentration of Esomeprazole（0.1,0.5 and 1.0 μg / ml） for 8 h.Reactive oxygen species（ROS） was measured by monitoring lucigenin- derived chemiluminescence.mRNA expression of heme oxygenase- 1（HO- 1） and cyclooxygenase（COX） were determined by real time PCR.The enzyme activity of HO-1 was detected by colorimetry and the protein expression level of HO- 1 was determined by Western blotting.Results After incubated for 8 h,Esomeprazole could significantly inhibit NAPDH induced ROS production,and 1.0 μg / ml Esomeprazole could decrease the ROS production by（73.3 ± 3.5） %.Real-time PCR results demonstrated that 0.5 and 1.0 μg / ml Esomeprazole could increase the HO- 1 mRNA to 8.2 and 38.4 fold,respectively.And Esomeprazole could also increase the enzyme activity of HO- 1 in AGS cells in dose- dependent manner.However,expression of COX- 1 and COX- 2 remained unaffected,and COX- inhibitors（30 μmol / L Naproxen or Rofecoxib） did not antagonize HO- 1 induction by Esomeprazole.Conclusion Esomeprazole exhibits antioxidant effect on gastric epithelial cells by up- regulating the expression of HO- 1.

关 键 词：埃索美拉唑 上皮细胞 胃 血红素氧化酶 环氧化酶 

分 类 号：R975.2[医药卫生—药品]