细胞凋亡与增殖失衡在小鼠大肠癌诱发过程中的作用  

The Effects of the Out of Balance of the Apoptosis and the Proliferation on the Large Bowel Carcinogenesis in Mice

作　　者：孙保存[1] 王岚[1] 赵秀兰[1] 李龙[2] 刘易欣[1] 闫雪燕[1] 王欣[1] 古强[1] 

机构地区：[1]天津医科大学病理学教研室 [2]天津市南开医院

出　　处：《中国肿瘤临床》2004年第1期45-49,共5页Chinese Journal of Clinical Oncology

基　　金：天津市自然科学基金项目资助(编号:973611311)

摘　　要：目的:观察小鼠大肠癌不同阶段中细胞增殖与凋亡的变化规律,探讨细胞增殖—凋亡失衡在大肠不同阶段中的作用。方法:利用二甲肼(DMH)皮下注射诱发昆明种小鼠实验性大肠癌动物模型,分别于诱癌12、18、24、32周分批处死动物,以DNA末端标记(TUNEL)和免疫组化PCNA染色分别标记凋亡细胞和增殖细胞,多阶段动态观察增殖细胞和凋亡细胞的分布和密度变化。结果:小鼠正常粘膜中凋亡细胞全部位于表层,增殖细胞位于基底,数量均很少。诱癌早期增殖细胞和凋亡细胞轻度增多,二者比值变化不大;诱癌中期二者密度均显著升高,比值变化不显;诱癌晚期非癌粘膜增殖和凋亡细胞密度高于其它时段,不典型增生粘膜中增殖细胞增多,且随其程度递增,而凋亡细胞虽有升高,但不随其程度变化,二者比值则随其程度呈下降趋势。结论:1)在动物模型上证实了小鼠大肠癌发生过程中存在细胞增殖—凋亡失衡;2)诱癌早期低增殖、低凋亡,中期高增殖、高凋亡,晚期(癌)极高增殖、低凋亡;3)增殖细胞随不典型增生程度递增,凋亡细胞变化不显,二者比值呈递增趋势;4)癌变阶段最本质的变化为凋亡/增殖比值极度降低。以上结果支持我们以前在人类大肠癌研究中提出的“细胞选择性增殖”假说。Objective:To observe the pattern of change of the proliferation and the apopto-sis in the different stages of the large intestine carcinoma in mice and explore the effects of the out of balance of the apoptosis and the proliferation on the different stages of the large intestine carcinogenesis.Methods:Using the experimental animal model of the large intestine carcinoma of the mice of KUNMING species induced by the subcuteneous injection of dimethylhydrazine(DMH),we observed the distribution and the density change of the proliferative and the apoptotic cells dynamically in a multistage way.The animals were killed in batches in the12 th ,18 th ,24 th ,and32th weeks of carcinoma induction seperately.And the apoptotic and the proliferative cells were labeled seperately using TUNEL and PCNA immunohistochemical staining methods.Results:In the normal mucosas of the mice,all the apoptotic cells were situated in the superficial layers,how ever,the pro liferative cells were situated in the basement layers,and the amounts of both of them were rare,In the early stage of the carcinoma induction,the proliferative and the apoptotic cells slightly in creased in amount,but there were no obvious changes in the ratio of them.In the medi um stage,the densities of both of them increased distinctly,but there were no obvious changes in the ratio.In the late stage,the densities of the proliferative and the apop totic cells in the non-carcinoma mu cosas were higher than those in other phases.The proliferative cells in-creased in the atypical hyperplastic mu cosas and increased progressively with the degree of the lesions.Al though the apop totic cells in creased,their changes were not with the degree of the le-sions.And the ratio of them showed a decreased tendency with the degree of the lesions.Conclu-sions:1)The presence of the out of balance of the cell proliferation and the apoptosis was con-firmed in the course of the large intestine carcinogenesis in a mice model.2)In the early Stage of the carcinoma in duction the proliferat

关 键 词：小鼠大肠癌 细胞凋亡 

分 类 号：R735.34[医药卫生—肿瘤]