应用活体生物发光成像技术研究纳米雄黄的抗小鼠恶性黑色素瘤肝肺转移作用  

Anti-metastatic Actions of Realgar Nanoparticles on Hepatic and Pulmonary Metastasis of Murine Malignant Melanoma with in vivo Bioluminescence Imaging System

作　　者：席晓霞[1] 席栋宾[2] 范临兰[1] 魏虎来[1] 

机构地区：[1]兰州大学基础医学院医学实验中心,甘肃省新药临床前研究重点实验室,兰州730000 [2]酒泉市人民医院,酒泉735000

出　　处：《实验动物与比较医学》2015年第5期345-350,共6页Laboratory Animal and Comparative Medicine

基　　金：中央高校基本科研业务费专项资金自由探索面上项目（LZujbky-2015-157）,甘肃省自然科学研究基金计划项目（1208RJZA183）和甘肃省中医药科学技术研究课题（GZK-2010-17）

摘　　要：目的采用小动物活体成像技术研究纳米雄黄对小鼠B16-luc恶性黑色素瘤的抗转移作用和机制。方法以萤火虫荧光素酶（1uciferase，luc）基因标志小鼠B16黑色素瘤细胞（B16-luc），BALB／c小鼠的尾静脉注射B16-luc细胞制作小鼠黑色素瘤肺转移瘤模型，每日4mg／kg和8mg／kg纳米雄黄灌胃24d，阳性对照组隔日腹腔注射顺铂（DDP）2mg／kg，阴性对照组灌胃生理盐水0．02L／kg。小动物活体成像系统动态观察肿瘤细胞转移情况。治疗末期处死动物，取出肺和肝，置活体成像系统下直接成像，并肉眼观察肺和肝表面转移瘤结节形成：另对肺、肝肿瘤组织作HE染色，光镜下观察组织形态变化。结果活体成像显示纳米雄黄可显著抑制小鼠黑色素瘤细胞在肺和肝中的转移（P〈0．05），解剖肉眼可见肝、肺表面转移灶显著减少或消失，病理学检查显示纳米雄黄治疗组小鼠的肺脏内转移瘤结节小、数量较少，大多数瘤结节中央呈坏死液化改变，肝脏内未见到转移瘤结节。结论纳米雄黄可有效抑制小鼠恶性黑色素瘤B16-luc细胞的肺转移和肝转移能力。Objective To study the anti-metastasis action and mechanisms of realgar nanoparticles （nano-realgar） on malignant melanoma B 16-luc cells in mice by application of in vivo bioluminescence imaging assay. Methods The firefly luciferase （luc） gene was transferred into murine B 16 melanoma cells with a lentiviral vector（B16-luc cells）. B16-luc cells were injected into tail vein of BALB/c mice to establish the pulmonary and hepatic melanoma metastasis model. The model mice were treated with 4 mg/kg and 8 mg/kg nano-realgar once a day by ig for 24 days, and the optical in vivo imaging system was used continuously and dynamically to observe the tumor metastatic situation in mice. At the end of the treating period the mice were sacrificed, and the lungs and liver were removed, and the fluorescence images of the organs were acquired directly with the optical in vivo imaging system, and the metastasis nodules on the lung and liver surface were also observed for perusal. Finally the lung, liver and tumor stained with HE staining, and the morphological changes were observed under microscope. Results Observation with optical in vivo imaging system showed that nano-realgar administration could markedly suppressed the pulmonary and hepatic metastasis of B 16-luc cells （P〈0.05）. ARer nanorealgar treatment, the numbers of pulmonary and hepatic metastasis nodules significantly reduced even disappeared, and pathological examinations revealed that, in the nano-realgar treated mice, the metastasis nodules in lungs seems small and little, the liquefactive necrosis appeared in the central area of most nodules, and no metastasis nodules was found in liver. Conclusion Realgar nanoparticles are able to inhibit significantly the abilities of pulmonary and hepatic metastasis of B 16-luc malignant melanoma cells in mice.

关 键 词：纳米雄黄 小鼠恶性黑色素瘤 活体成像技术 

分 类 号：R739.5[医药卫生—肿瘤]