Hahm K B, Lee K J, Kim J H, Cho S W, Chung M H
Department of Gastroenterology, Ajou University School of Medicine, Suwon, Korea.
Dig Dis Sci. 1998 Sep;43(9 Suppl):72S-77S.
Several epidemiological studies have demonstrated a close association between Helicobacter pylori infection and carcinoma of the mid- or distal stomach. If this can be shown to be a causal association, eradication of the organism may prevent later development of cancer. Several mechanisms have been proposed by which H. pylori infection might lead to predisposition for gastric cancer. Although many potential pathogenic mechanisms, such as increased proliferative gastric epithelial response to H. pylori, lowered gastric ascorbic acid levels, and high occurrences of atrophic gastritis, have been proposed, there is little evidence as to which might be of direct importance to such H. pylori-related disease in vivo. H. pylori-associated inflammation may interact with other causal factors related to gastric carcinogenesis and can result in the intestinal type of gastric cancer and then DNA damage due to oxygen radicals induced by persistent inflammatory cell infiltrations in the gastric mucosa may lead to alterations of the gene and result in the development of diffuse-type carcinoma. In order to know the influence of H. pylori on changes of inflammation-related DNA damage, we measured the sequential changes of 8-hydroxydeoxyguanosine (8-OHdG) contents of DNA and the changes of two biomarkers inducible nitric oxide synthase (iNOS) and apoptosis from human gastric mucosa according to the status of H. pylori. The increased levels of oxidative DNA damage, increased occurrences of apoptosis, and increased expressions of iNOS seem to provide the mechanistic links between H. pylori infection and gastric carcinogenesis and rebamipide can abrogate the levels of these hazard factors.
多项流行病学研究表明，幽门螺杆菌感染与胃中或胃远端癌之间存在密切关联。如果能证明这是一种因果关系，根除该病菌可能会预防后续癌症的发生。已经提出了几种幽门螺杆菌感染可能导致胃癌易感性的机制。尽管已经提出了许多潜在的致病机制，如胃上皮细胞对幽门螺杆菌的增殖反应增加、胃内抗坏血酸水平降低以及萎缩性胃炎的高发病率，但几乎没有证据表明哪种机制在体内对此类幽门螺杆菌相关疾病可能具有直接重要性。幽门螺杆菌相关炎症可能与其他与胃癌发生相关的因果因素相互作用，并可导致肠型胃癌，然后由于胃黏膜中持续炎症细胞浸润诱导的氧自由基导致DNA损伤，可能会导致基因改变并导致弥漫型癌的发生。为了了解幽门螺杆菌对炎症相关DNA损伤变化的影响，我们根据幽门螺杆菌的状态，测量了人胃黏膜DNA中8-羟基脱氧鸟苷（8-OHdG）含量的连续变化以及两种生物标志物诱导型一氧化氮合酶（iNOS）和细胞凋亡的变化。氧化DNA损伤水平的增加、细胞凋亡发生率的增加以及iNOS表达的增加似乎提供了幽门螺杆菌感染与胃癌发生之间的机制联系，瑞巴派特可以消除这些危险因素的水平。
