不同性别PyMT自发性乳腺癌小鼠成瘤特点和不同时间肺转移观察

Tumorigenic Characteristics of PyMT Mice with Spontaneous Breast Cancer in Different Genders and Observation of Pulmonary Metastasis in Different Time

[目的]研究不同性别自发性乳腺癌小鼠乳腺肿瘤病毒启动子(mouse mammary tumor virus,MMTV)控制下表达多瘤中间T抗原(polyoma middle T-antigen,Py MT)的转基因小鼠的致瘤特性,再以雌性小鼠为观察对象进一步研究血常规指标变化及肺转移情况等。[方法]准备同为8周龄的Py MT雌性小鼠和Py MT雄性小鼠,观察比较雌性与雄性小鼠肿瘤发病时间、生存时间与生存率;另取同为8周龄的雌性Py MT和雌性FVB小鼠,观察8周后取血进行血常规检测,并通过病理切片观察小鼠12周龄及16周龄时肺组织的病理变化。[结果]每周观测小鼠的形态学特征可发现雌鼠第8周可扪及肿瘤,而雄鼠则在第18周可扪及肿瘤;雌鼠最长生存时间是19周,雄鼠则为46周,即雌性小鼠肿瘤发病时间早于雄性小鼠,生存时间明显短于雄性小鼠。血常规指标检测显示,雌性Py MT小鼠白细胞及亚群(除单核外)数量明显高于FVB小鼠(P<0.05,P<0.001);雌性Py MT小鼠在12周龄开始出现肺转移,肺部大量炎症细胞浸润,16周时肺组织伊红染色法(hematoxylin-eosin staining,HE)染色发现明显的肺转移,出现弥漫性分布、大小不等、质实、染色深的癌巢,细胞间推挤或重叠,细胞大小形态不同。[结论]MMTV-PyMT自发性乳腺癌小鼠雌鼠发病比雄鼠早,生存时间短,具有实验周期短、便于观察肿瘤发生的优势,12周龄开始出现肺转移,16周龄肺转移明显,是适合用于筛选抑制肿瘤细胞浸润、转移等药物的乳腺癌动物模型。本实验还通过血常规结果、肺转移情况数据为实验动物性别的选择提供参考。

[Objective]To further study the tumorigenic characteristics of transgenic mice expressing the polyoma middle T-antigen(PyMT)under the control of the mouse mammary tumor virus(MMTV)promoter of different genders,and to further the changes of blood routine indexes and pulmonary metastasis in female mice.[Methods]5 PyMT female mice and 5 PyMT male mice,aged 8 weeks,were chosen to observe tumor growth,survival time and survival rate of female and male mice;5 PyMT female and 5 FVB female mice were taken for routine blood test after 8 weeks of observation,and pathological changes of lung tissue in mice were observed by pathology in 12 and 16 weeks old.[Results]The morphological characteristics of the mice were observed every week,and tumor can be touched when female mice were 8 weeks old and male mice were 18 weeks old;female mice lived for up to19 weeks,while male mice lived for up to 46 weeks,so female mice developed tumors earlier than male mice,and their survival time was significantly shorter than that of male mice.Blood routine tests showed that the number of leukocytes and subgroups(except monocytes)in PyMT female mice was significantly higher than that in FVB female mice(P<0.05,P<0.001).PyMT female mice began to develop lung metastasis at 12 weeks of age.Lung metastasis was found by hematoxylin-eosin staining(HE)of lung tissue,appearing diffused distribution,different sizes,solid and deep stained cancer nests,pushing or overlapping between cells,and different cell sizes and morphology.[Conclusions]The female mice of MMTV-PyMT developed spontaneous breast cancer earlier than the male mice,had a shorter survival time,had the advantages of short experimental cycle,and were easy to observe the tumor genesis.Lung metastasis began at 12 weeks old,and was obvious at 16 weeks old.It was an animal model of breast cancer suitable for screening of traditional Chinese medicine in inhibiting tumor cell infiltration and metastasis.Furthermore,the results of this study can be used as a reference for sex selection,blood routine results and lung metastasis data were also used to provide references for the selection of animal sex.