基因转导心脏的方法学研究  

A study on the methodology of gene transfering into heart

作　　者：李建军[1] 李庚山[1] 黄从新[1] 夏豪[1] 许家俐[1] 王晶 王腾[1] 

机构地区：[1]湖北医科大学第一附属医院心内科,湖北武汉430060

出　　处：《中华老年心脑血管病杂志》1999年第1期35-37,共3页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：国家教委 !( 19986 79);国家人事部 !( 199813)基金资助项目

摘　　要：目的　探讨经自制针型导管心肌内注射 (下称心肌注射法 )、经冠状动脉灌注 (下称冠脉灌注法 )及经心房穿刺心包 (下称心包注射法 ) 3种方法导基因入心脏的可行性及利与弊。方法　选成年杂交犬 1 5只 ,将含有同等剂量携带有细菌lacZ基因的重组腺病毒载体 (约 1× 1 0 9pfuAdex1SRLacZ) ,经心肌注射法、冠脉灌注法及心包注射法 3种方法导基因入心脏。术后 3d处死动物 ,组织化学法分析lacZ基因在心包及心肌中的表达。结果　冠脉灌注法导基因入心脏后 ,lacZ基因在心肌中呈点或小片状表达 ;心肌注射法导基因入心脏后 ,lacZ基因沿注射轨迹成块或片状表达 ,心包注射法基因导入心包后 ,犬心包脏层、壁层及脏层下心肌均可见散在的lacZ基因表达 ,而使用同样的 3种方法注射对照腺病毒 (Adexlw)至犬心肌及心包 ,均未见lacZ基因表达 ;心肌注射法导基因入心脏的同时 ,心肌中可见有明显的炎性细胞浸润 ,而冠脉灌注法及心包注射法导基因入心脏后则未见心肌中炎性细胞浸润 ;冠脉灌注法导基因入心脏的同时 ,肝脏组织中检测有散在的lacZ基因表达 ,而心肌注射法及心包注射法则不然。结论　心肌注射法、冠脉灌注法及心包注射法这 3种导基因法是基因导入心脏的可行性方法 ,且各有利弊 。Objective To investigate the feasibility and features of three main approaches to transfer a gene into heart in vivo, including direct myocardial injection(DMI) using a home made catheter,coronary artery perfusion (CAP) and transatrial pericardial sac injection (TPSI). Methods 0.3m1 of recombinant adenovirus vector(Adex 1SR LacZ)containing l×10 9 pfu was injected into the heart by using the three different gene delivery methods respectively ( n =5 for each method)in fifteen mongrel dogs.The dogs were killed 3 days following gene transfer,and gene expression in both heart and liver was evaluated by histochemical analysis.Results The results showed that CAP method did relatively 1ess damage and could induce sparse LacZ expression in myocardium,and gene expression was a1so found in vessels of myocardium and liver;The gene expression by DMI resulted in intensive LacZ expression in myocardium, which was accompanied by local inf1ammatory response;The LacZ expression by TPSI was detected in both inner surface of parietal pericardium and epicardial surface of the heart,and also observed in the myocardium underneath visceral pericardium in a patchy manner. Conclusion The results indicated that the three methods concerning gene transferring into the heart in vivo used in the present study were useful, and a reasonable approach should be chosen according to the purpose of gene transferring into the myocardium in vivo.

关 键 词：腺病毒 心肌基因导入 心包基因治疗 

分 类 号：R654.2[医药卫生—外科学]