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目的系统观察胃粘膜肠化生的形成及其发展趋势以及病变过程中癌相关基因蛋白表达。方法应用低浓度甲硝基亚硝基胍 (MNNG)及抑酸剂雷尼替丁联合喂饲，辅以胃部间断 X线照射方法建立 Beagle(毕格 )犬胃粘膜肠化生动物模型。运用免疫组化法对胃粘膜活检组织 APC、 p53、 K-ras、 bcl-2基因蛋白表达进行了分析。结果运用 MNNG＋雷尼替丁＋局部 X线照射方法成功地建立了毕格犬胃粘膜肠化生模型，采用此模型动态观察胃粘膜病变过程，证实了正常→浅表胃炎→萎缩胃炎→灶状肠化→中重度肠化变化规律。并发现癌基因 bcl-2蛋白在萎缩性胃炎中即可表达，在肠化组织中可检出抑癌基因 APC、癌基因 K-ras蛋白表达。结论 MNNG＋雷尼替丁＋局部 X线照射是建立毕格犬胃粘膜肠化生模型有效方法。犬胃粘膜肠化生经历了与人体相似变化过程。癌相关基因 bcl-2、 APC、 K-ras蛋白在犬胃粘膜肠化生及癌变中可能起一定作用。
Objective To systematically observe the formation and development of intestinal metaplasia of gastric mucosa and the expression of cancer-associated gene protein during the course of lesions. Methods Gastrointestinal metastasis model of Beagle dogs was established by low concentration of nitroguanidine (MNNG) combined with ranitidine, an inhibitor of acid, and intermittent intermittent X-ray of the stomach. The expression of APC, p53, K-ras, and bcl-2 genes in gastric biopsies was analyzed by immunohistochemistry. Results The gastric mucosal intestinal metaplasia model was established successfully using MNNG + ranitidine and local X-ray irradiation. This model was used to observe the pathological changes of gastric mucosa dynamically, confirming normal → superficial gastritis → atrophic gastritis → focal shape. Intestinal → moderate and severe intestinal changes. It was found that the oncogene bcl-2 protein can be expressed in atrophic gastritis, and the expression of the tumor suppressor gene APC and oncogene K-ras protein can be detected in the intestinal metaplasia. Conclusions MNNG + ranitidine plus local X-ray irradiation is an effective method to establish intestinal metaplasia model in Beagle dogs. Intestinal metaplasia of canine gastric mucosa undergoes similar changes with the human body. The cancer-related genes bcl-2, APC, and K-ras proteins may play a role in intestinal metaplasia and carcinogenesis in dogs.