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目的:建立各方面更接近人类的小细胞肺癌(SCLC)动物模型,为SCLC的基础和临床研究提供参考。方法:以非人灵长类动物食蟹猴作为实验动物,经切除脾脏后,通过支气管镜直接注入人类SCLC细胞株Nci-h446至食蟹猴的支气管黏膜,诱导建立人SCLC的食蟹猴模型。通过胸部CT扫描和经支气管镜活检送病理,鉴定模型建立的成功率。结果:人小细胞肺癌食蟹猴模型的建立所需时间最少需要9个月,但最早约6个月即能发现细胞水平的变化(核异质变)。食蟹猴模型的生活状态、生化水平及影像学改变都与人类肺癌的发病过程相似。6只食蟹猴成功生长出肺癌的有3只,模型建立成功率为50%。按接种部位计算,12个接种细胞浓度为1×107 mL-1的位点,成功生长出肺癌的3个,成功率为16.7%;接种细胞浓度为1×107 mL-1的位点,出现细胞核异质以上改变(包括癌变)的5个,占41.7%;但接种细胞浓度为1×105 mL-1和接种细胞浓度为1×106 mL-1的位点,成功率为0。所有36个接种位点成功率为8.3%,出现细胞核异质以上改变(包括癌变)的百分率为13.9%。结论:通过支气管镜直接接种人类SCLC细胞株Nci-h446至食蟹猴的支气管黏膜,能成功建立人SCLC的食蟹猴模型,但细胞浓度至少达1×107 mL-1。
Objective: To establish an animal model of small cell lung cancer (SCLC) that is closer to human beings in all respects and provide a reference for basic and clinical research of SCLC. Methods: Non-human primate cynomolgus monkeys were used as experimental animals. After excision of the spleen, bronchial mucosa of human SCLC cell line Nci-h446 was injected directly into bronchial mucosa of cynomolgus monkey by bronchoscopy to establish a cynomolgus monkey model of human SCLC . The success rate of model establishment was identified by chest CT scan and bronchoscopic biopsy. Results: It took at least 9 months to establish the model of human SCLC cynomolgus monkey, but the change of cell level (nuclear heterogeneity) could be found in about 6 months at the earliest. Cynomolgus monkey model of life status, biochemical levels and imaging changes are similar to the pathogenesis of human lung cancer. Three cynomolgus monkeys successfully developed lung cancer, with a model success rate of 50%. According to the site of inoculation, 12 sites of 1 × 107 mL-1 cells were successfully inoculated and 3 of lung cancers were successfully established with a success rate of 16.7%. The site of inoculation at a concentration of 1 × 107 mL-1 appeared Five of the above changes (including carcinogenesis) were nuclear heterogeneity, accounting for 41.7%. However, the inoculation cell concentration was 1 × 105 mL-1 and the inoculum cell concentration was 1 × 106 mL-1. The success rate was 0. The success rate of all 36 vaccination sites was 8.3%, with a 13.9% increase in nuclear heterogeneity (including carcinogenesis). CONCLUSIONS: Human SCLC cynomolgus monkey model can be successfully established by direct inoculation of bronchial mucosa of human SCLC cell line Nci-h446 into cynomolgus monkey with bronchoscopy, but the cell concentration is at least 1 × 107 mL-1.