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目的 观察甲基硝基亚硝基胍 (N methyl N′ nitro N nitrosoguanidin ,MNNG)对裸鼠异种移植人胚胃粘膜的影响。方法 用MNNG直接诱导移植于裸鼠体内的人胚胃粘膜 ,HE和AB/PAS染色观测胃粘膜组织形态 ,链霉菌抗生物素蛋白 -过氧化物酶免疫组化 (SP)法检测胃粘膜PCNA、C erbB 2、p53表达状态。结果 对照组人胚胃粘膜的存活率为 72 % (18/ 2 5) ,实验组为 56 % (9/ 16 ) ,两组动物最长存活期为 9个月。移植 3～ 4个月后 ,人胚胃粘膜的生长发育在形态、结构和功能上基本与正常胃粘膜一致。实验组 9只检出轻度异型增生 2只、中度 4只、重度 2只。免疫组化染色证实 ,实验组 9只胃粘膜PCNA均存在不同程度的阳性 ,其程度随着异型增生病变加重而增强。在中度和重度异型增生的胃粘膜中发现C erbB 2阳性 2只 ,1只p53阳性见于重度异型增生的胃粘膜中。结论 MNNG可直接诱发人胃粘膜的癌前期病变 ,并导致C erbB 2、p53基因的过度表达和 /或突变。这些变化可能对筛选胃癌目标人群有着一定价值
Objective To observe the effect of MNNG on human gastric mucosa in nude mice xenografts. Methods The gastric mucosa of human embryo transplanted in nude mice was induced directly with MNNG. The morphology of gastric mucosa was observed by HE and AB / PAS staining. The expression of PCNA was detected by streptavidin-peroxidase immunohistochemistry (SP) , C erbB 2, p53 expression status. Results The survival rate of human gastric mucosa was 72% (18/25) in control group, 56% (9/16) in experimental group, and the longest survival time was 9 months in both groups. 3 to 4 months after transplantation, human gastric mucosal growth and development in morphology, structure and function of the basic and normal gastric mucosa. Nine of the experimental group detected mild dysplasia 2, moderate 4, severe 2. Immunohistochemical staining confirmed that the experimental group of 9 gastric mucosal PCNA were present in varying degrees of positive, with the degree of dysplasia increased. In moderate and severe dysplasia gastric mucosa found in C erbB 2 positive 2, one p53 positive found in severe dysplasia of the gastric mucosa. Conclusion MNNG can directly induce precancerous lesions of human gastric mucosa and lead to overexpression and / or mutation of C erbB 2 and p53 genes. These changes may have some value in screening gastric cancer target population