肺癌转移瘤动物模型的建立

目的通过尾静脉注射,建立一种符合临床特征的肺腺癌转移瘤动物模型,为下一步的肺腺癌转移机制的研究提供可靠的实验造模方法。方法取对数生长期的A549细胞,11只SPF级、4~6周龄BALB/c裸鼠,分别以1×106个细胞/只注射入裸鼠尾静脉。接种后每天观察小鼠状态。分别于接种肿瘤细胞后第4、5、6、7周随机处死2只,余3只小鼠处于濒死状态时处死。解剖小鼠,观察肺部有无转移、转移结节的数目及全身其他器官的转移情况,并做病理取材,HE染色观察。结果注射过程中小鼠均存活。未处死的3只分别于第11、13、14周出现恶液质。第4周肺部未见转移结节;第5周出现镜下肺部转移结节;第6周肉眼可见肺部转移结节;第7周转移结节数增多;第11周出现纵隔淋巴结转移。第11、13、14周出现肺部结构大量破坏,弥漫性的肿瘤细胞浸润,出现淋巴结浸润,病理证实为腺癌。结论通过尾静脉注射A549细胞可以成功建立人肺腺癌转移瘤模型。

Establishment of a nude mouse model of pulmonary adenocarcinoma metastasis

Objective To establish an optimal animal model of pulmonary metastasis of human lung adenocarcino-ma, to serve further investigation of mechanism of lung adenocarcinoma metastasis.Methods Eleven nude mice aged 4-6 weeks were used in this study.Suspension of human lung adnocarcinoma A549 cells （0.1 mL, 107 cells/mL） was injec-ted into the tail vein in nude mice.From four weeks after inoculation, two nude mice were killed each time at 4, 5, 6 weeks after the tumor cell injection at random for examination.The remaining 3 mice were killed at the end of the experi-ment.At autopsy, the lung, brain, liver, kidney and other organs were removed, fixed in neutral buffered formalin and embedded in paraffin.Sections were cut and stained with hematoxylin-eosin, and examined by histopathology.The number of metastatic foci was counted.Results No mouse died after tumor cell inoculation.Serially euthanized mice revealed evi-dence of gradually increasing pulmonary metastases in the mice：No metastasis was found before 4 weeks after tumor cell in-oculation, the first histological metastases appeared at 5 weeks, gross metastatic foci were observed at 6 weeks, widely spread metastatic foci were observed at 7 weeks, and the remain 3 mice developed cachesia at 11, 13, and 14 weeks after tumor cell inoculation.Mediastinal lymph node metastases were found in the nude mice by 11 weeks after tumor cell inocu-lation.Conclusions We have successfully established a nude mouse model of pulmonary metastasis by injecting human lung adenocarcinoma A549 cells into the tail vein.