人脑转移癌组织裸小鼠脑内移植模型的建立

Establishment of orthotopic transplantation model of metastatic carcinoma masses of human brain in nude mice

目的建立人肺腺癌脑转移瘤的裸小鼠原位移植模型，并分析移植瘤的生物学特征。方法取人肺腺癌脑转移瘤组织块，接种于裸小鼠右尾状核。致瘤后即用裸小鼠的瘤组织进行其原位传代接种，观察致瘤率及荷瘤鼠生存期；MRI观察移植瘤在鼠脑内的大体形态；HE染色分析各代移植瘤的组织学形态；免疫组化染色观察移植瘤中CEA的表达；Alcian blue／PAS特殊染色检测移植瘤中粘液的性质。结果移植瘤组织在裸小鼠右尾状核已连续传至6代，共65只鼠。荷瘤鼠生存期：原代为（47．6±1．8）d，2～3代有所缩短，4～6代稳定在（38．0±0．9）d；移植瘤MRI类圆形，瘤周无水肿。移植瘤病理为低分化腺癌，不向周围正常鼠脑组织浸润；移植瘤中CEA表达阳性，有酸性粘液存在。结论人肺腺癌脑转移瘤组织块接种于鼠脑内建立的原位移植模型能更好地模拟临床原发肿瘤的病理学特征，本方法为研究人肺腺癌脑转移瘤的生物学特性及实验治疗提供了一个可靠的动物模型。

Objective To establish an orthotopic transplantation model of brain metastasis of human lung adenocarcinoma in nude mice and analyze its biological features. Methods Human brain metastatic tumor masses were collected and orthotopicly transplanted into the right caudate nucleus of nude mice. The newly formed xenografts were sharply minced into pieces and re-transplanted. The efficiency of tumorigenicity and the survival time of tumor-bearing mice were observed. HE staining and MRI scanning were performed to investigate the histopathological and imaging features of this metastatic lesion. The expression of tumor marker （CEA） and mucin in xenografts was also investigated using immunohistochemical staining or Alcian blue/PAS assays. Results The brain xenografs in the right caudate nucleus were passed mice to the 6th generation in a total of 65 nude mice,with average survival time of tumor-bearing mice （47.6±1.8） d for primary generation and （38.0±0. 9 ） d for （4 - 6） generation, respectively. Histopathologically, the cerebral xenografts were poorly differentiated andenocarcinoma without invasiveness to normal brain tissue. MRI revealed a well-delimitated mass without surrounding edema, which perfectly recapitulated the original tumor. Expression of CEA and acid mucin was positive in the cerebral xenografts. Conclusions The orthotopic xenografts of brain metastasis from human lung andenocarcinoma could faithfully recapitulate the original tumor clinically and pathologically, and provides a reliable animal model not only for the study on the biological features but also for the experimental on treatment of brain metastasis from lung adenocarcinoma.