酸性成纤维细胞生长因子基因转染改善缺血心肌血流灌注的研究  

The improvement of myocardial perfusion after gene transfer of ac idic fibroblast growth factor into swine chronic ischemic myocardium

作　　者：顾俊彦[1] 梅举[1] 黄盛东[1] 徐志云[1] 张宝仁[1] 蔡凯华[1] 朱泉芳[1] 

机构地区：[1]第二军医大学长海医院胸心外科实验室,上海200433

出　　处：《中华实验外科杂志》2003年第4期298-299,共2页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金资助项目 (39970 735)

摘　　要：目的　探讨酸性成纤维细胞生长因子 (aFGF)基因重组腺病毒 (Ad .aFGF)转染改善缺血心肌血流灌注的作用。方法　小型猪左冠回旋支 (Lcx)放置Ameroid环后 4周 ,注射Ad .aFGF(n =7)、空病毒 (Ad .Null,n =6 )、磷酸盐缓冲液 (PBS ,n =6 )于Lcx供血区域 ,每头 10点 ,每点 1× 10 9pfu或 10 0 μl的PBS。 4周后 ,单光子计算机断层扫描 (SPECT )和心脏超声分别检测局部血流灌注和心功能。注射点心肌Ⅷ因子免疫组织化学染色观察血管新生。结果　SPECT显示Ad .aFGF组心肌核素摄取评分 ( 76 .1± 2 .9)显著高于Ad .Null组 ( 6 4.6± 3 .0 ,P <0 .0 1)和PBS组( 6 5 .4± 3 .9,P <0 .0 1) ;超声显示Ad .FGF组节段性室壁收缩期增厚率 ( 34.1± 1.8) %显著高于Ad .Null组 [( 2 4.2± 2 .3) % ,P <0 .0 1]和PBS组 [( 2 3 .7± 2 .2 ) % ,P <0 .0 1] ;免疫组织化学显示Ad .aFGF组心肌中血管密度 [( 32 .8± 1.9)个 /每高倍视野 (HPF) ]显著高于Ad .Null组 [( 18.2±1.5 )个 /HPF ,P <0 .0 1]和PBS组 [( 17.3± 1.7)个 /HPF ,P <0 .0 1]。结论　Ad .aFGF转染慢性缺血心肌可增加血流灌注 ,改善心功能。s Objective To investigate the improveme n t of myocardial perfusion after gene transfer of acidic fibroblast growth factor (aFGF) into swine chronic ischemic myocardium.Methods Ex perimental mini swine underwent thoracotomy and placement of an Ameroid constric tor on the left circumflex coronary artery (Lcx).Four weeks later,Ad.aFGF (n =7),Ad.Null (n=6) or PBS (n=6) was administrated directly into the myoca rdium at 10 sites in the circumflex distribution area (1×109 pfu or 100 μl). Four weeks later,myocardial perfusion and function were assessed by 99 KG *3/4 mTc-sestamibi single photon emission computed tomography imaging (SPECT) and echocardiography respectively.After amimals were sacrificed and hearts were harvested,new blood vessels at injection sites were examined by Factor Ⅷ immuno histological labeling.Results SPECT demonstrated a signif icant revival of myocardial perfusion in the ischemic areas in Ad.aFGF-treated animals (76.1± 2.9) as compared with Ad.Null- (64.6± 3.0,P <0.01) a nd PBS (65.4±3.9,P<0.01) treated animals.Meanwhile,echocardiography docume nted a significant improvement of myocardial function in Ad.aFGF-treated animal s (34.1± 1.8)% as compared with the other groups [Null:(24.2±2.3)%, P<0.01],[PBS:(23.7±2.2)%,P<0.01].Ⅷ immunohistological staining s howed new blood vessels were much more in Ad.aFGF group (32.8±1.9/HPF) than the other two groups [Null:(18.2±1.5)/HPF,P<0.01],[PBS:(17.3±1.7)/HPF, P<0.01].Conclusion Direct intramyocardial administrat ion of Ad.aFGF results in the improvement of myocardial perfusion and function.

关 键 词：酸性成纤维细胞生长因子 腺病毒载体 心肌缺血 基因转染 

分 类 号：R363[医药卫生—病理学]