肺癌颅脑转移动物模型建立的比较

Comparison Between the Establishment Methods of Mouse Models of Lung Cancer Brain Metastases

目的通过左心室注射、尾静脉注射、胸腔注射3种方法,建立肺癌颅脑转移的动物模型。方法18只BALB/c NUDE裸鼠随机分为三组,分别经左心室注射、尾静脉注射、胸腔注射途径,接种具有颅脑转移潜能的人肺腺癌PC-9细胞(1×10^(6)/0.1 mL),接种后观察裸鼠状态,在裸鼠出现恶病质时处死;解剖裸鼠,肉眼观察肺和颅脑的转移情况,并对其进行HE染色处理。结果左心室注射组:裸鼠注射后18 d开始出现体质量下降,逐步出现恶病质,并于27 d将裸鼠全部处死;解剖观察肺、颅脑无异常;HE染色证实,肿瘤病灶并未在它们的肺部发现;6只裸鼠均有共济失调、偏瘫、跛行的症状,是颅脑转移的病灶引起的。尾静脉注射组:注射后55 d裸鼠体质量开始减轻,92 d开始出现恶病质,处死于112 d;解剖观察肺、颅脑无异常;HE染色证实4只裸鼠身上出现肺部肿瘤灶;6只裸鼠均未发现颅脑转移。胸腔注射组:裸鼠于注射后22 d出现胸壁瘤结;35 d开始有消瘦,恶病质渐起,42 d处死;解剖观察肺部、胸腔见多发肿瘤结节,并胸膜、肋骨、脊柱浸润;HE染色证实6只裸鼠全部表现为肺部转移;6只裸鼠均未发现颅脑转移。结论左心室注射组脑转移率为100%,肺癌颅脑转移动物模型建立的可靠方法是经左心室注射途径。

Objective To establish an appropriate animal model of brain metastases from lung cancer in nude mice by left ventricular injection,tail vein injection,thoracic orthotopic implantation in the chest.Methods A total of 18 BALB/c NUDE nude mice were randomly divided into 3 groups,which were inoculated with human lung adenocarcinoma PC-9 cells(1×10^(6)/0.1 mL)with brain metastasis potential through left ventricular injection,tail vein injection,and thoracic injection,respectively.The status of nude mice was observed after inoculation,and the nude mice were killed when they showed abnormal fluid.The nude mice were dissected,the lung and brain metastases were observed by naked eye,and HE staining was performed.Results In the left ventricular injection group,the body mass of the nude mice began to decline on the 18th day after injection,and the abnormal fluid gradually appeared,and all the nude mice were killed on the 27th day.No abnormality was observed in lung and brain by anatomy.HE staining confirmed that tumor lesions were not found in their lungs.All the 6 nude mice had symptoms of ataxia,hemiplegia and claudication,which were caused by brain metastases.In the tail vein injection group,the body mass of nude mice began to decrease at 55 days after injection,and the abnormal fluid began to appear at 92 days after injection,and the mice were killed at 112 days after injection.No abnormality was observed in lung and brain by anatomy.HE staining confirmed the presence of lung tumors in 4nude mice.No brain metastasis was found in 6 nude mice.In the thoracic injection group,the nodule of the chest wall was found 22 days after injection.On the 35th day,he began to emaciate,the bad fluid gradually developed,and he was killed on the 42nd day.Multiple tumor nodules were observed in the lung and chest,and pleural,rib and spinal infiltration were observed.HE staining showed lung metastasis in all 6 nude mice.No brain metastasis was found in 6 nude mice.Conclusion The rate of brain metastases from lung cancer in the left ventricular injection group was 100%.The pathway of injecting into left ventricular is a good method for establishing the brain metastatic animal models.