甲基硝基亚硝基胍对裸鼠异种移植人胚胃粘膜的影响

Effects of MNNG on the Xenografted Human Embryonic Gastric Mucosa in Nude Mice

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。

WT5BZ]Objective: [WT5BZ]To investigate effects of N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) on the xenografted human embryonic gastric mucosa in nude mice. Methods: [WT5BZ]MNNG was utilized to attack directly the human embryonic gastric mucous which has been xenografted in nude mice. HE and AB/PAS staining were used to observe the morphology and structure of the xenografted human embryonic gastric mucosa in mude mice. Expression of PCNA、C-erbB-2 and p53 in the xenografted human embryonic gastric mucosa were proved by Streptavidin-Peroxidase (SP) immunohistochemical method. Results:[WT5BZ]The rate of viability of controlled group was 72% (18/25), that of the experimental group was 56% (9/16). The xenografted human embryonic gastric mucosa in both groups maintained 9 months ultimately. Development and growth of the gastric mucosa which had been xenografted in nude mice before 3 to 4 months were consistent with the normal human gastric mucosa in the morphology, structure and functions. 2 cases were slight atypical hyperplasia, 4 cases were intermediate and 2 case were heavy in the 9 trial human gastric mucus. 9 cases were PCNA positive to some extent in the trial group, moreover, its extent of positive increased in consistent with the lesion of the atypical hyperplasia. In the cases of intermediate atypical hyperplasia and heavy 2 cases were C erbB 2 positive. In the cases of heavy atypical hyperplasia 1 case was p53 positive by the SP immunohistochemistic staining. Conclusion: [WT5BZ]MNNG can induce directly precancerous lesions in human gastric mucosa and can also result in C erbB 2, p53 gene overexpression or mutation, such aterations may be applicated to screen the target population of stomach carcinoma.