小动物活体成像系统Spectrum-CT在人肺癌裸鼠原位移植瘤模型建立中的应用  

Application of small animal in vivo imaging system Spectrum-CT in establishing orthotopic model of human lung cancer in nude mice

作　　者：安国 许辉 张文龙 宋祎萍 李勇[1] An Guo;Xu Hui;Zhang Wenlong;Song Yiping;Li Yong(Department of Laboratory Animal,Peking University Cancer Hospital&Institute,Peking University School of Oncology,Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education),Beijing 100142,China)

机构地区：[1]北京大学临床肿瘤学院,北京大学肿瘤医院暨北京市肿瘤防治研究所实验动物室恶性肿瘤发病机制及转化研究教育部重点实验室,100142

出　　处：《肿瘤研究与临床》2020年第4期250-255,共6页Cancer Research and Clinic

基　　金：国家自然科学基金(30871366);北京市自然科学基金(7152029)。

摘　　要：目的应用小动物活体成像系统Spectrum-CT对3种不同方式建立的人肺肿瘤裸鼠原位移植瘤模型进行实时监测和生物学特性比较,为肺癌研究提供更有价值的实验动物模型。方法构建稳定表达荧光素酶的人肺癌A549细胞株(A549-Luc),应用胸腔注射法、尾静脉注射法和气管灌流法将A549-Luc细胞分别接种于裸鼠(每组6只),建立人肺癌原位移植瘤模型。应用Spectrum-CT活体成像系统对3组模型鼠进行生物发光成像,监测肿瘤组织的生长情况和荧光信号强度,每周1次,连续监测4周,最后解剖裸鼠肺组织进行体外发光成像和病理学分析。结果生物发光成像分析结果显示,3种模型鼠移植瘤组织均持续生长,建模第4周,胸腔注射组模型鼠的荧光信号强度值[(2.78±0.18)×106 P/s]强于气管灌流组[(1.45±0.20)×106 P/s]和尾静脉注射组[(1.35±0.14)×106 P/s](F=62.53,P<0.01);3D活体成像分析显示,3组模型鼠肺癌移植瘤组织呈不同的生长状态,胸腔注射法模型鼠呈右侧肺叶接种位点处单点肿瘤灶生长,气管灌流法模型鼠肿瘤灶呈左右两侧肺叶不确定多点生长模式,尾静脉注射法模型鼠肿瘤灶相对较为均匀地分布在左右两侧肺叶上。结论与气管灌流法和尾静脉注射法模型鼠比较,胸腔注射法原位肺肿瘤模型成瘤更快,在开展移植瘤主动定位研究方面存在优势;结合使用Spectrum-CT活体成像系统,在原位肺肿瘤模型建立的早期阶段就可以对移植瘤组织的生长情况进行实时定位和定量分析,可为肺癌发病机制和药学研究提供有价值的实验材料。Objective To provide more valuable experimental animal models for lung cancer research,three kinds of orthotopic human lung neoplasms models in nude mice were established and their biological characteristics were monitored and compared by using small animal in vivo imaging system Spectrum-CT.Methods Human lung cancer A549 cell line stably expressing luciferase(A549-Luc)was constructed and three kinds of orthotopic human lung cancer models in nude mice(6 mice/each group)were established by means of intrapleural injection,tail vein injection and tracheal perfusion with A549-Luc cells,respectively.Additionally,bioluminescence imaging was performed on model mice by using Spectrum-CT imaging system to monitor the growth of tumor tissues and the intensity of fluorescence signal once a week for 4 consecutive weeks.Finally,the lung tissues of model mice were dissected for in vitro bioluminescence imaging and pathological analysis.Results The results of bioluminescence imaging analysis revealed that the transplanted tumor tissues of all three groups continued to growth.At the 4th week after cell inoculation,the fluorescence signal intensity of the mice in the intrapleural injection group[(2.78±0.18)×106 P/s]was significantly higher than that in the tracheal perfusion group[(1.45±0.20)×106 P/s]and the tail vein injection group[(1.35±0.14)×106 P/s](F=62.53,P<0.01).The 3D in vivo imaging analysis showed that the tumor tissues had different growth states in three orthotopic lung cancer models.The intrapleural injection model had a single tumor focus at the inoculation site of the right lung lobe.The tumor tissues of the tracheal perfusion model showed an uncertain multi-point growth pattern in the left and right lung lobes.In the tail vein injection model,the tumor foci were relatively evenly distributed in the left and right lobes.Conclusions Compared with the tracheal perfusion model and the tail vein injection model,the intrapleural injection orthotopic lung cancer model shows stronger tumorigenic ability and has adv

关 键 词：肺肿瘤 模型 动物 荧光素酶 生物发光成像 

分 类 号：R-332[医药卫生] R734