携带绿色荧光蛋白腺病毒经不同给药方式进入BALB／C鼠体内后的组织分布和代谢  

Characterization of the kinetics of viral distribution and spread after different injections of adenovirus Adv-GFP in a BALB/C mice model

作　　者：黄晓园[1] 庄亮[1] 曹阳[1] 高庆蕾[1] 袁劲[2] 马丁[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院肿瘤生物医学中心,武汉430030 [2]华中科技大学同济医学院附属同济医院器官移植研究所

出　　处：《中华实验外科杂志》2009年第5期585-587,F0003,共4页Chinese Journal of Experimental Surgery

基　　金：国家重大基础研究（973）计划资助项目（2002CB513109）

摘　　要：目的观察重组腺病毒分别经由尾静脉和腹膜后注射进入小鼠体内后的组织分布和代谢，探讨重组腺病毒载体与肝移植结合治疗肝癌的可行性和安全性。方法分别采取尾静脉和腹膜后注射Adv—GFP建立动物模型，以绿色荧光蛋白（GFP）表达作为指示观察腺病毒的组织分布；用原位杂交法比较各器官的腺病毒转录；定量检测注射后不同时间点血清和肝脏中的病毒滴度。结果两种不同给药方式注射Adv—GFP入小鼠体内后，在基因转录与GFP表达上均显示Adv—GFP主要分布在肝、脾、肺和肾；腹膜后注射与尾静脉注射比较，肝组织内腺病毒转录与表达明显增多（P〈0．05），而脾、肺和肾有不同程度的减弱；腹膜后注射的腺病毒亦会短时内进入体循环，但肝组织的病毒滴度在1周内各个时间点均明显高于尾静脉途径。结论重组腺病毒腹膜后注射能够优化治疗效果，并在一定程度上减少全身反应，更适于肝癌肝移植后的基因治疗。Objective To explore the kinetics of viral distribution and spread in a BALB/C mice model after the intravenous infusion or retroperitoneal infusion, and evaluate the safety of reconstructed adenovirus administration with liver transplantation in hepatocellular carcinoma therapies. Methods BALB/ C mice were intravenously or retroperitoneally injected with purified Adv-GFP in order to make animal models. The expression of green fluorescence protein （GFP） and the adenovirus mRNA was detected by using fluorescence assay and in situ hybridization. The virus in serum and liver was tittered at the indicated time point. Results The expression of GFP and adenovirus mRNA was both located preferentially in the liver, spleen,lung and kidney by two methods of infusion in mice. There were more adenovirus vectors in the liver after the retroperitoneal infusion than those after intravenous infusion. Though there was virus dissemination into the general circulation at early time points after retroperitoneal infusion, the amount of virus in the liver was more in one week than that after intravenous infusion. Conclusion The retroperitoneal infusion of adenovirus vectors may achieve more satisfactory effectiveness and reduce systemic reaction to some extent, which is more suitable for gene therapy.

关 键 词：肝移植 腺病毒 分布 基因治疗 

分 类 号：R735[医药卫生—肿瘤]