幽门螺杆菌长期感染蒙古沙土鼠建立胃癌模型的研究

Development of gastric adenocarcinoma in mongolian gerbils after long-term infection of Helicobacter pylori

目的 幽门螺杆菌 (Hp)长期感染导致蒙古沙土鼠 (MGs)发生胃癌鲜见报道。本实验旨在研究Hp长期定植于MGs导致胃黏膜病变及其致癌性。 方法 36只远交封闭群MGs(雌雄各半 )分别接种Hp标准株ATCC4 35 0 4 ,或从胃癌患者胃内分离的Hp16 1株 ,10只MGs作为对照。接种后第8、2 0、2 8和 84周分别处死 ,检查细菌定植及胃黏膜病变情况。结果 绝大多数MGs胃内Hp持续定植 ,胃黏膜炎症随时间逐渐加重。第 84周组织学特征是胃黏膜中～重度胃炎 ,以淋巴细胞为主的单核细胞弥漫性浸润 ,黏膜、黏膜下 ,甚至浆膜下有大量淋巴滤泡浸润 ,偶见淋巴上皮病变 ,萎缩、肠化较少见。上皮增生明显 ,2 4 % (4/ 17)发生增生性息肉 ,第 84周时 18% (3/ 17)发生高分化腺癌 (Hp16 1组 1例 ,ATCC4 35 0 4组 2例 ;1雄 2雌 )。结论 单独感染Hp能诱导MGs发生胃癌 ,并提示可利用不同种属的MGs和不同Hp菌株进行相关研究。

Objective The experimental evidences that long term colonization of H. pylori results in development of gastric cancer in Mongolian gerbils (MGs) have been reported only by two Japanese groups so far. This study aimed to investigate the carcinogenicity of long term H. pylori infection in MGs model. Methods Thirty six 6 week old outbred MGs (from Inner Mongolia, male∶female=1∶1) were orally inoculated with H.pylori ATCC43504 or H.pylori 161, which was isolated from a patient with gastric adenocarcinoma in our hospital. Another 10 MGs were inoculated with sterilized PBS served as controls. The animals were sacrificed 8, 20, 28 and 84 weeks, respectively, after inoculation for bacteria and histological examination. Results H.pylori was detected in 80%(23/29)of the inoculated MGs and the chronic active gastritis aggravated gradually during the course of experiment. At the 84th week, moderate to severe gastritis, characterized by diffuse infiltration of mononuclear cells and formation of multiple lymphoid follicles in the mucosa and submucosa, and even the lymphocytic epithelial lesions were observed. Atrophy and intestinal metaplasia were less common. The lesions of hyperplasia were dominating in almost all MGs, 24%(4/17)of the animals occurred hyperplastic polyps. Well differentiated gastric adenocarcinomas were developed in 18% (3/17) of the MGs by the end of the 84th week (1 infected with H.pylori 161 and 2 with H.pylori ATCC43504, two of them were female MGs). Conclusions The results reconfirm that H.pylori infection alone can cause gastric adenocarcinoma in MGs. It is suggested that different species of MGs and various strains of H.pylori can be utilized for carcinogenesis research. It is the first report of the development of gastric cancer in female MGs, which might make sense of investigation on the host susceptibility influenced by gender.