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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 and distribution of luciferase in Ad-Luci transfected mice by different routes of injection, and to provide a reference for gene therapy of adenovirus vector. Methods: The model of human pancreatic cancer cell line PANC-1 was established in nude mice. The Ad-Luci virus was injected intratumorally or in vivo intratumorally or intra-peritoneally and intraperitoneally to Ad-Luci virus in normal mice. IVIS Lumina Live imaging system to observe the distribution and expression of luciferase in mice, and to observe the toxicity of Ad-Luci virus. Results: A single intratumoral injection of Ad-Luci luciferase in the tumor sustained expression of 15 d, after repeated intratumoral injection of expression longer. The expression of luciferase in the intramuscular injection group decreased with time, and no luciferase was detected 48 h after injection. Most of the luciferase in the tail vein injection group was accumulated in the liver, and was still expressed on the 18th day after injection. Luciferase expression was observed 4 h after intraperitoneal injection, but no expression was observed after 7 d. Ad-Luci mice in each injection group showed no significant toxicity. Conclusion: The adenovirus carrying exogenous gene can be expressed in tumor for a long time by intratumoral injection. Multiple injections can prolong the expression time. After injection through the tail vein, it mainly accumulates in the liver and expresses for a long time.