中文摘要：

背景与目的：环氧合酶2（cyclooxygenase-2，COX-2）是花生四烯酸转化为前列腺素（prostaglandins，PGs）代谢中重要的限速酶，幽门螺杆菌（Helicobacterpylori，Hp）感染诱导胃黏膜COX-2的过度表达是胃癌发生的重要环节，但Hp感染胃黏膜细胞COX-2表达的机制尚不清楚。本研宄旨在揭示Hp对人胃癌MKN45细胞COX-2表达和Hp38MAPK信号通路的影响，探讨COX-2表达的可能机制。方法：采用实时荧光定量PCR（teal time-PCR）检测Hp标准株NCTC11637感染对人胃癌MKN45细胞COX-2 mRNA转录的影响，Westernblot检测坳COX-2蛋白表达的影响和p38MAPK信号通路的激活及其下游因子ATF-2的表达。结果：Hp感染人胃癌MKN45细胞后，COX-2 mRNA的表达明显上调，Hp感染3、6、9、12h后COX-2 mRNA的表达量分别为正常值的3倍、7．2倍、5．1倍和4．3倍，各时间组COX-2 mRNA表达均明显高于对照组（P〈0．01）；Hp与MKN45细胞共培养24h后，COX-2蛋白的表达亦显著增加（P〈0．01）。Hp感染MKN45 20min后，p38MAPK信号通路被激活，60min达峰值；p38MAPK下游因子ATF2的表达也明显增加，2h达高峰，随着作用时间的延长，表达逐渐下降，24h仍有表达。结论：坳感染能诱导人胃癌MKN45fm胞COX-2的表达；激活p38MAPK信号通路，增加其下游因子ATF2的表达，可能是其诱导COX-2表达的机制。

英文摘要：

Background and purpose： Cyclooxygenase-2 （Cyclooxygenase-2, COX-2） is an important rate-limiting enzyme that is responsible for transformation of arachidonic acid into prostaglandins（PGs）. Although Helicobacter pylori（Hp） infection-induced gastric over-expression of COX-2 （COX-2） is an important factor of gastric cancer, the mechanism of COX-2 expression in gastric mucosa cells infected with Hp is still not clear. Our study was to reveal the effect of Hp on expression of COX-2（cyclooxygenase-2）, the impact of p38MAPK signaling pathway in human gastric epithelial cancer cells line MKN45, and to investigate the potential mechanisms of expression of COX-2. Methods： The expression of COX-2 mRNA infection by standard Hp NCTC 11637 in human gastric epithelial cancer cells line MKN45 was evaluated by real-time fluorogenic quantitative polymerase chain reaction （RFQ-PCR）.The effect of infection by Hp on COX-2 expression, activation of p38MAPK and its downstream of the ATF-2 was assayed by Western blot. Results： The expression of COX-2 mRNA in MKN45 cells infected by Hp compared with control group,COX-2 mRNA had 3 fold, 7.2 fold, 5.1 fold, 4.3 fold up-regulation after 3 hrs, 6 hrs, 9 hrs, 12 hrs, respectively. COX-2 mRNA expression in each time group was significantly higher than that in the control group（P〈0.01）. MKN45 cells were co-cultured with Hp for 24 hrs, COX-2 protein expression also increased significantly（P〈0.01）. Hp inducedactivation of p38MAPK after 20 min and the expression was the highest when at 60min.The expression of p38MAPK downstream factor ATF-2 also increased significantly, and was the highest when at 2 hrs. With extended time, the expression gradually declined and was still expressed after 24 hrs. Conclusion： Hp can induce the expression of COX-2 mRNA and protein in human gastric cancer cells line MKN45, activate p38MAPK signal pathway, and increase the expression of its downstream factor ATF-2, that maybe one of the important mechanisms of COX-2 expression