Kodama Masaaki, Fujioka Toshio, Murakami Kazunari, Okimoto Tadayoshi, Sato Ryugo, Watanabe Koichiro, Nasu Masaru
Department of General Medicine, Faculty of Medicine, Oita University, Hasama-machi, Oita 879-5593, Japan.
J Gastroenterol Hepatol. 2005 Jun;20(6):941-6. doi: 10.1111/j.1440-1746.2005.03880.x.
Although Helicobacter pylori has been regarded as a pathogen of gastric cancer, the mechanism by which H. pylori is involved in gastric carcinogenesis remains unknown. To clarify the role of H. pylori in carcinogenesis, the expression of tumor suppressor p53 and its regulator multiple double minute 2 (MDM2) in gastric mucosa were examined before and after H. pylori eradication.
Biopsy specimens were obtained from 31 patients with H. pylori-infected gastric mucosa. Endoscopic biopsies were repeated 6 months after successful eradication. In addition, biopsy specimens from 12 patients with non-infected gastric mucosa were obtained. Immunohistochemical analysis was performed on the specimens using primary antibodies specific for p53 and MDM2.
Six months after H. pylori eradication, labeling indices for p53 were significantly reduced in the gastric corpus (2.3-fold; P < 0.01), and in the gastric antrum (2.0-fold; P < 0.01). Similarly, labeling indices for MDM2 were significantly reduced in the corpus (1.7-fold; P < 0.01), and in the antrum (3.5-fold; P < 0.01). In the non-infected group, labeling indices for p53 and MDM2 in the gastric mucosa were significantly lower (P < 0.01) than those of the H. pylori-infected group.
A significant increase is shown in p53 and MDM2 expression in H. pylori-infected gastric mucosa as compared to normal gastric mucosa; but successful eradication of H. pylori dramatically reduced the p53 and MDM2 levels. Therefore, H. pylori infection may be associated with alteration of cell proliferation and apoptosis.
尽管幽门螺杆菌已被视为胃癌的病原体，但幽门螺杆菌参与胃癌发生的机制仍不清楚。为了阐明幽门螺杆菌在致癌过程中的作用，在幽门螺杆菌根除前后检测了胃黏膜中肿瘤抑制因子p53及其调节因子多聚双微体2（MDM2）的表达。
从31例幽门螺杆菌感染的胃黏膜患者中获取活检标本。在成功根除幽门螺杆菌6个月后重复进行内镜活检。此外，还获取了12例未感染胃黏膜患者的活检标本。使用针对p53和MDM2的特异性一抗对标本进行免疫组织化学分析。
幽门螺杆菌根除6个月后，胃体部p53的标记指数显著降低（2.3倍；P < 0.01），胃窦部也显著降低（2.0倍；P < 0.01）。同样，胃体部MDM2的标记指数显著降低（1.7倍；P < 0.01），胃窦部降低更为明显（3.5倍；P < 0.01）。在未感染组中，胃黏膜中p53和MDM2的标记指数显著低于幽门螺杆菌感染组（P < 0.01）。
与正常胃黏膜相比，幽门螺杆菌感染的胃黏膜中p53和MDM2表达显著增加；但成功根除幽门螺杆菌可显著降低p53和MDM2水平。因此，幽门螺杆菌感染可能与细胞增殖和凋亡的改变有关。
