腺病毒载体介导的TPO基因疗法对放射损伤小鼠造血功能重建的影响  

Thrombopoietin gene therapy mediated by recombinant adenovirus vector on hemopoietic reconstitution of mice injured by 5 Gy γ irradiation

作　　者：刘林[1] 张曦[1] 罗成基[2] 粟永萍[2] 陈幸华[1] 

机构地区：[1]第三军医大学新桥医院血液科,重庆400037 [2]第三军医大学防原医学教研室,重庆400038

出　　处：《重庆医学》2005年第9期1286-1288,共3页Chongqing medicine

基　　金：重庆市应用基础研究基金资助课题(2002)

摘　　要：目的研究腺病毒载体介导的TPO基因疗法对放射损伤小鼠造血功能重建的影响.方法将构建的TPO腺病毒经(AdCMVTPO)腹腔注射至5Gy放射损伤小鼠体内,并与注射空载体(AdCMVNull)相对照,检测外周血WBC、Hb及PLT的动态变化.结果空载体注射组于照射后产生严重的全血细胞下降:PLT于照后6～12d降至200×109/L以下,WBC于照后6～15d降至1.0×109/L以下,Hb于照后12～15d降至6.0g/L以下.AdCMVTPO治疗组PLT降低的程度减轻,其最低值高于200×109/L(P<0.05,与对照组最低值比较),且提早约2周恢复接近正常.同时也有一定程度的加速WBC和Hb恢复的作用.结论腺病毒载体介导的TPO基因疗法可显著促进放射损伤小鼠PLT的恢复,对Hb、WBC的恢复也具有一定的促进作用.Objective To study the thrombopoietin gene therapy mediated by recombinant adenovirus vector on hemopoietic reconstitution of mice injured by irradiation. Methods Replication-deflcient mouse thrombopoietin （TPO） cDNA recombinant adenoviruses （AdCMVTPO） was injected through intraperitoneal in the mice injured by 5.0Gy γirradiation, taken AdCMVNull as control. WBC, Hb and PLT were examined during the course. Results In animals receiving the AdCMVNull, the radiation induced a profound pancytopenia with the nadir of WBC bellow 1.0 × 10^9/L from 6d to 15d, Hb bellow 6.0g/L from 12d to 15d, and PLT bellow 200 × 10^9/L from 6d to 12d. When AdCMVTPO was administered immediately after irradiation, the platelet levels were sustained, with a nadir above 200 × 10^9/L at 6d （P〈0.05 compared to control at nadir）. Further, the recovery to normal levels was accelerated by approximately two weeks. Interestingly, there was a trend towards accelerated recovery of the WBC, as well as the Hb. Conclusion The TPO gene therapy mediated by adenovirus vector could mainly accelerate the recovery of PLT and had some extent effect on the recovery of WBC and Hb.

关 键 词：腺病毒栽体 促血小板生成素 基因治疗 造血功能重建 

分 类 号：R818[医药卫生—放射医学]