活体成像系统检测携荧光素酶增殖缺陷型腺病毒在小鼠体内的表达和分布  

In vivo imaging system in detecting expression and distribution of replication-deficient adenovirus carrying luciferase in mice

作　　者：孟希亭[1] 林晨[1] 梅佳[1] 王海娟[1] 马飞[1] 张金龙[1,2] 张颖[3] 钱海利[1] 

机构地区：[1]中国医学科学院北京协和医学院肿瘤医院肿瘤研究所暨分子肿瘤学国家重点实验室,北京100021 [2]潍坊医学院附属医院肿瘤科,山东潍坊261031 [3]首都医科大学附属北京妇产科医院微创科,北京100020

出　　处：《中国肿瘤生物治疗杂志》2011年第4期389-393,共5页Chinese Journal of Cancer Biotherapy

基　　金：国家高科技研究发展计划(863计划)资助项目(No.2007AA021001);国家自然科学基金资助项目(No.30772527)~~

摘　　要：目的:研究携带荧光素酶的增殖缺陷型腺病毒(Ad-luciferase,Ad-Luci)经不同途径注射后小鼠体内荧光素酶的表达和分布,为肿瘤的腺病毒载体基因治疗提供参考。方法:建立人胰腺癌PANC-1细胞裸鼠移植瘤模型,Ad-Luci病毒单次或多次瘤体内注射,或者肌内、尾静脉和腹腔注射Ad-Luci病毒至正常小鼠,采用IVIS Lumina活体成像系统观察荧光素酶在小鼠体内的分布和表达,并观察Ad-Luci病毒的毒性作用。结果:单次瘤内注射Ad-Luci荧光素酶在瘤内持续表达15 d,多次瘤内注射后表达时间更长。肌内注射组荧光素酶随时间延长表达减弱,注射后48 h无荧光素酶表达。尾静脉注射组荧光素酶大部分聚集在肝脏,注射后18 d仍有表达。腹腔注射组4 h后可见荧光素酶的表达,但7 d后无表达。Ad-Luci各注射组小鼠均未出现明显的毒性反应。结论:腺病毒携带外源基因经瘤内注射可在瘤内表达较长时间,多次注射可延长表达时间;经尾静脉注射后主要聚集在肝脏,且表达时间较长。Objective： To study the expression of luciferase in mice delivered by replication-deficient adenovirus carrying luciferase（Ad-luciferase,Ad-Luci） through different injection routes,so at to provide information for adenovirus-mediated tumor gene therapy.Methods： Nude mouse model bearing human pancreatic cancer PANC-1 cells was established and Ad-Luci was administered into transplanted tumors with single or multiple intratumoral injections.Ad-Luci was also administered into normal mice through intramuscular,intravenous and intraperitoneal injections.The distribution and expression of luciferase in mice were monitored by in vivo IVIS Lumina imaging system and the toxicity of Ad-Luci was also studied.Results： Single intratumoral injection of Ad-Luci resulted in continuous luciferase expression for at least 15 d,while multiple injections resulted in even longer expression.Intramuscular injection of Ad-Luci gave a weaker and shorter duration of luciferase expression for no longer than 48 h.The majority of Ad-Luci injected through tail-vein homed to liver and expressed luciferase for at least 18 d.Expression of luciferase by intraperitoneal injection decreased with time-lapse and lasted for about 7 d.No significant toxic reactions were observed in all groups during the study.Conclusion： Intratumoral injection of adenovirus carrying exogenous gene gives a continuous expression of gene for a long duration,while multiple injections result in even longer expression;liver is the main target organ after tail intravenous administration and provides long expression duration.

关 键 词：腺病毒载体 胰腺癌 荧光素酶 活体成像系统 基因治疗 

分 类 号：R735.9[医药卫生—肿瘤] R730.5[医药卫生—临床医学]