犬胃粘膜肠上皮化生模型的建立及其肠化过程中癌相关蛋白的表达

Experimental induction of intestinal metaplasia in stomach＆ expression of tumor-related proteins

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 The development and progression of intestinal metaplasia ( IM ) and expression of tumor-related proteins in dog’ s stomach were observed. Methods IM animal model was established in Beagle’ s stomach by feeding N-methyl-N’-nitro-N-trosoguanidine( MNNG ),ranitidine,and local X-irradiation. Expression of APC, p53, K-ras and bcl-2 genes in canine gastric lesion were determined by immunohistochemistry. Resullts IM canine model was successfully induced, with which sequential pathology studied. It was proved that progression of normal epithelial cells to IM cells might undergo several stages including superficial gastritis, chronic atrophic gastritis, mild focal IM, moderate,and severe IM.Aberrant bcl-2 protein was detected in atrophic gastric epithelium and abnormal expression of APC, K-ras, and bcl-2 found in IM mucosa. Conclusion Canine gastric IM was induced by the method mentioned above.The development of normal gastric mucosa to IM in dog seemed to resemble that of human being.The presence of tumor-related proteins might indicate the transformation of IM to malignancy.