中文摘要：

背景与目的：血管内皮生长因子（vascular endothelial growth factor，VEGF）是重要的促血管生成因子，幽门螺杆菌（Helicobacter pylori，H. pylori）感染诱导胃黏膜VEGF过表达是胃癌生长、转移的重要环节，但其表达机制尚不清楚。环氧化酶-2（cyclooxygenase-2，COX-2）是一种快速反应蛋白，与胃癌发生发展关系密切。本研究旨在探讨COX-2对H. pylori诱导胃癌细胞VEGF表达的影响，揭示H. pylori感染促进胃癌生长、转移的部分机制。方法：采用实时荧光定量PCR（RFQ-PCR）法检测标准H. pylori（NCTC 11637细胞株）感染人胃癌MKN45细胞VEGF的表达；Western印迹法检测H. pylori对MKN45细胞中COX-2蛋白表达的影响；运用COX-2特异性抑制剂NS398（50 μmol/L）抑制COX-2后，观察H. pylori对MKN45细胞VEGF mRNA表达的影响。结果：H. pylori感染人胃癌MKN45细胞后VEGF mRNA的表达明显上调。H. pylori感染6、12和24 h后VEGF mRNA的表达量分别为正常值的2.33（P〈0.05）、5.69和5.04倍（P〈0.01）；H. pylori感染MKN45细胞24 h后，COX-2蛋白的表达亦显著增加（P〈0.01）。而采用COX-2特异性抑制剂NS398抑制COX-2的表达后，H. pylori诱导的VEGF mRNA表达明显降低（P〈0.01）。结论：H. pylori感染诱导胃癌细胞COX-2和VEGF表达，通过COX-2途径上调VEGF的表达，这可能是H. pylori感染促进胃癌生长、转移的重要机制之一。

英文摘要：

Background and purpose：Vascular endothelial growth factor （VEGF） is an important proangiogenic factor, and Helicobacter pylori （H. pylori） infection-induced gastric over-expression of VEGF is an important factor of gastric cancer growth and metastasis, but its expression mechanism is not clear. Cyclooxygenase-2（COX-2） is a rapid response protein, which is closely related to the occurrence and development of gastric cancer. Our study was to investigate the effect of COX-2 on H. pylori-induced VEGF expression in human gastric cancer cells, and to reveal part of the mechanism of gastric cancer growth and metastasis promoted by H. pylori infection. Methods： The expression of VEGF mRNA in human gastric epithelial cells （MKN45） infected by standard H. pylori NCTC 11637 and the expression of COX-2 protein were evaluated by real-time fluorogenic quantitative polymerase chain reaction （RFQ-PCR） and assayed by Western blot. After inhibiting COX-2 expression with COX-2 specific inhibitor NS398 （50 μmol/L）, VEGF mRNA expression induced by H. pylori in human gastric cancer MKN45 cells was evaluated by RFQ-PCR. Results：H. pylori significantly stimulated the expression of VEGF mRNA in MKN45 cell line. Compared with control MKN45 cells; VEGF mRNA had 2.33 fold up-regulation after 6 h （P〈0.05）; and had 5.69 and 5.04 fold upregulation respectively after 12 and 24 h （P〈0.01）.When MKN45 cells were infected with H. pylori for 24 h, COX-2 protein expression also increased significantly （P〈0.01）, and after inhibiting the COX-2 expression with COX-2 specific inhibitor NS398, H. pylori-induced VEGF mRNA expression was significantly reduced. Conclusion：H. pylori could induce the expression of COX-2 and VEGF in human gastric cancer cells, and could enhance VEGF expression by COX-2 pathway, which might be one of the important mechanisms of gastric cancer growth and metastasis promoted by H. pylori infection.