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.

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）