幽门螺杆菌对CCAAT增强子结合蛋白α和Cx43表达的影响及其在胃癌发生中的作用

目的：探讨CCAAT增强子结合蛋白α(CCAAT enhancer binding protein α，C/EBPα)和间隙连接蛋白43(connexin 43，Cx43)表达改变在H. pylori致胃癌中的作用。方法：扩大培养不同胃黏膜上皮细胞株(GES-1细胞、AGS细胞、SGC-7901细胞)；胃镜下采集H. pylori感染慢性非萎缩性胃炎患者6例、胃癌前病变和胃癌患者各12例胃黏膜组织；采用real-time PCR法检测上述细胞和组织中C/EBPα和Cx43 mRNA的表达；同时将东亚型CagA+H. pylori与GES-1细胞共培养24和48 h为实验组，以不加H. pylori的GES-1细胞株为对照组，培养24和48 h；采用real-time PCR法和Western印迹检测C/EBPα和Cx43 mRNA和蛋白的表达。结果：C/EBPα和Cx43 mRNA在AGS细胞、SGC-7901细胞中的表达均显著低于GES-1细胞(均P<0.05)，且两者在SGC-7901细胞中的表达量较AGS细胞更低(均P<0.05)；C/EBPα和Cx43 mRNA在胃癌胃黏膜组织中的表达明显低于慢性非萎缩性胃炎(均P<0.05)和胃癌前病变(均P<0.05)，C/EBPα与Cx43表达呈正相关(胃癌前病变：r=0.679；胃癌：r=0.792，均P<0.05)；实验组24，48 h的 C/EBPα和CX43表达量在转录及蛋白水平均低于对照组(均P<0.05)，且48 h表达量均低于24 h(均P<0.05)。结论：H. pylori感染可下调胃黏膜上皮细胞C/EBPα和CX43的表达，这可能与胃癌发生有关。

Effect of H. pylori on the expression of CCAAT enhancer binding protein α and Cx43 and its role#br# in gastric carcinogenesis

Objective: To explore the effect of H. pylori on the expression of CCAAT enhancer binding protein α (C/EBPα) and connexin 43 (Cx43) in gastric carcinogenesis. Methods: Different gastric mucosal epithelial cell lines (GES-1 cells, AGS cells and SGC-7901 cells) were cultured. A total of 6 cases of chronic non-atrophic gastritis tissues, 12 cases of gastric precancerous lesions tissues and 12 cases of gastric cancer tissues were collected under endoscopy. The expression of C/EBPα and Cx43 mRNA in the above-mentioned cells and tissues was detected by real-time PCR. The GES-1 cells and East Asian CagA+ H. pylori strains were co-cultured for 24 and 48 h as an experimental group, and those cell lines without H. pylori infection were cultured for 24 and 48 h as a control group. Real-time PCR and Western bolt were used to detect the expression of mRNA and proteins of C/EBPα and Cx43 in GES-1 cells, respectively. Results: The expressions of C/EBPα and Cx43 mRNA in the AGS and SGC-7901 cells were lower than those in GES-1 cells (all P<0.05), and both of them decreased more profoundly in the SGC-7901 cells than those in the AGS cells (both P<0.05). The expressions of C/EBPα and Cx43 mRNA were lower in the gastric cancer tissues than those in the chronic non-atrophic gastritis tissues (both P<0.05) and gastric precancerous lesion tissues (both P<0.05). The C/EBPα expression was positively correlated with Cx43 expression (gastric precancerous lesion tissues: r=0.679, gastric cancer tissues: r=0.792; both P<0.05). Compared with the control group, the expressions of C/EBPα and Cx43 mRNA and protein in the experimental group were decreased at 24 and 48 h after culture (both P<0.05), which were lower at 48 h than those at 24 h (both P<0.05). Conclusion: H. pylori infection can down-regulate the expressions of C/EBPα and Cx43 on gastric epithelial cells, which may be associated with gastric carcinogenesis.