腺相关病毒介导的心肌基因转染在心脏移植中的应用

Adeno-Associated Virus(AAV) mediated gene delivery to myocardium in heart transplantation

目的:探讨在不同转导方法下,将外源性基因转入供体心脏的可行性。方法:将携带报告基因半乳糖苷酶基酶(LacZ)的病毒载体经三种办法转导供体心脏方法:直接心肌注射法,经冠状动脉单次灌注法,组织胺预处理+经冠状动脉单次灌注法。心脏移植21 d后,供体心脏进行组织学检查,分析报告基因转染和表达。结果:经冠状动脉单次灌注法,组织胺预处理+经冠状动脉单次灌注法处理的两组移植心脏中未发现有报告基因的表达,直接心肌注射法组的移植物中发现有高效表达的报告基因。结论:在非生理状态下,经冠状动脉单次灌注病毒载体不能有效转染外源性基因,直接心肌注射法在心脏移植中是可行的。

Objective： To explore different methods for delivery exogenous gene into donor myocardium. Methods： AAV-Lack was applied in the experiment by three methods： direct injection into myocardium, single-pass intraocoronary infusion, pretreatment of histamine prior to intracoronary infusion. Graft was harvested at 21 days post- transplantation and transduction efficiency was determined by histological examination. Results： No transgenic was observed in the graft perfused with vector via intracoronary infusion; however, high transduction efficiency was achieved in the graft directly injected with vector. Conclusion： In nonphysiological status, it is difficult to transfer extrogenous gene to myocardinm by means of intracoronary infusion of vectors, while direct injection of virus into myocardium appears to feasibility in transplantation setting.