基于靶向转铁蛋白受体的荧光探针在原位胶质瘤动物模型的研究  

Application of fluorescent probe targeting transferrin receptor in glioma orthotopic animal models

作　　者：赵义营 蔡海平 陈银生 王静[1] 陈芙蓉[1] 陈忠平[1] 

机构地区：[1]中山大学附属肿瘤医院神经外科/神经肿瘤科,广州510060

出　　处：《中华神经外科杂志》2018年第2期188-193,共6页Chinese Journal of Neurosurgery

基　　金：国家重点基础研究发展计划（973计划）（2015CB755505）;广州市协同创新基金（201508020125）

摘　　要：目的 探究靶向转铁蛋白受体的荧光探针在原位胶质瘤动物模型上的应用价值.方法 将人胶质瘤细胞株U87转染表达荧光素酶的慢病毒H113,构建稳定表达荧光素酶的U87-MGH113稳定细胞株.在15只小鼠尾状核头部接种U87-MG H113细胞.接种3周后,腹腔注射荧光素酶底物,在小动物活体成像仪上采用荧光素酶专用检测通道检测确定成瘤.将确定成瘤的12只动物模型按随机数字表法随机分为PBS组、Cy5-CRT组、Cy5-CG7C组3组,尾静脉分别注射200μ10.1 mol/L的PBS、Cy5-CRT、Cy5-CG7C,注射24、36、48 h后在小动物活体成像仪上采用Cy5专用检测通道检测.结果 （1）成功构建了稳定表达荧光素酶的细胞株,并且证实单位时间内检测到的信号强度与细胞数量的多少成线性关系;（2）在成像效果最好的36 h时间段,3组的荧光信号强度分别为5.78±0.16（PBS组）、44.16 ±0.33（Cy5-CRT组）、5.34±0.17（Cy5-CG7C组）,Cy5-CRT组明显强于PBS组和Cy5-CG7C组,差异有统计学意义（P ＜0.005）.结论 Cy5-CRT光学探针在胶质瘤处聚集,与正常脑组织有很好的区分性,具有潜在的临床应用价值.Objective To validate the specificity of CRT-Cy5 peptide in glioma animal model and provide experimental basis for its clinical application.Methods The human glioma cell line U87 was transfected with lentivirus H113 to obtain U87-MG H113 that stably expressed luciferase.The U87-MG H113 cells were injected into the caudate nuclei of mice.After 3 weeks,the signal of luciferase was detected by small animal imaging instrument after intraperitoneal injection of luciferin to testify U87-MG H113 glioma model.Twelve animals of orthotopic glioma were divided into PBS,Cy5-CRT,Cy5-CG7C groups according to random number table.PBS,CyS-CRT and Cy5-CG7C （all in a dose of 0.1 mol/L,200 μl） were intravenously injected into the mice of each group.The signal of luciferase was detected by small animal imaging instrument after intraperitoneal injection of luciferin.The Cy5 signal was detected at 24 h,36 h,48 h post injection.Results （1） We successfully established cell lines that stably expressed luciferase whose intensity was positively correlated with the number of cells.（2） Three weeks later,12 animals of orthotopic glioma were divided into PBS,CyS-CRT,CyS-CG7C groups.At 36 h post injection,the signal of luciferase of PBS,Cy5-CRT,Cy5-CG7C groups was 5.78 ± 0.16、44.16 ± 0.33、5.34 ± 0.17,respectively.Signal analysis showed an 8 times increase of Cy5 signal intensity in Cy5-CRT group than the other 2 groups （P 〈 0.005）.Conclusion Cy5-CRT optical probe is enriched in glioma tissues rather than normal brain tissues and has potential values of clinical application.

关 键 词：神经胶质瘤 分子探针 模型 动物 转铁蛋白 分子影像学 

分 类 号：R-332[医药卫生] R739.4