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 -1 mRNA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 ep-ithelial 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,re-spectively. 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.
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