转染VEGF_(165)基因的自体成肌细胞治疗心肌梗死的实验研究  

Transplantation of autologous myoblasts transfected with VEGF_(165) improves heart function after myocardial infarction in rabbits

作　　者：庄炜[1] 李莉[2] 章庆春[3] 林国强[1] 邓震宇[1] 

机构地区：[1]中南大学湘雅医院心胸外科,长沙410008 [2]中南大学湘雅医院重症医学科,长沙410008 [3]安徽省立医院心血管外科,合肥230001

出　　处：《中南大学学报（医学版）》2012年第7期682-688,共7页Journal of Central South University ：Medical Science

基　　金：湖南省科技厅资助项目(2010SK3095)~~

摘　　要：目的:将体外培养、纯化并转染VEGF165基因的新西兰兔自体骨骼肌成肌细胞植入心肌梗死区,观测转染VEGF165基因的成肌细胞移植对改善梗死区心肌血运重建和心功能的影响。方法:采用pcDNA3.1-VEGF165和pcDNA3.1质粒转染经体外培养及纯化的新西兰兔自体骨骼肌成肌细胞。结扎兔冠状动脉致局部心肌梗死后2周,分别于心肌梗死区移植转染VEGF165基因成肌细胞(实验组,n=8)和空载体成肌细胞(对照组,n=8),4周后观察心肌梗死边缘区毛细血管密度、植入细胞的形态鉴定和心功能改善情况。结果:成功将pcDNA3.1-VEGF165和pcDNA3.1质粒转染体外培养的兔自体骨骼肌成肌细胞,成肌细胞移植后能在梗死区种植成活、分化。实验组细胞移植区域的毛细血管密度较对照组高(P<0.05)。经Buxco系统有创心功能测定显示:实验组较对照组的左心室等容收缩期室内压最大上升速率[+dp/dtmax,(1607.23±102.67)mmHg/s vs(1217.77±89.91)mmHg/s]和左心室等容舒张期室内压最大下降速率[-dp/dtmax,(1535.09±81.34)mmHg/s vs(1174.58±91.50)mmHg/s]均有所改善。结论:转染VEGF165的成肌细胞能改善心肌梗死区域的血液供应,增加心肌收缩力,改善心功能。Objective： To determine the improvements of post-infarction heart function after transplantation of autologous skeletal myoblasts transfected with VEGF165 in rabbits. Methods： Myocardium infarction was induced in rabbits by left anterior descending coronary artery ligation. At 2 weeks, 1.75×107 autologous skeletal myoblasts transfected with pcDNA3.1-VEGF165 were infused into the region of MI via direct intramuscular iniection; pcDNA3.1 served as a control. Results： The DAPI-labeled and Desmin-positive immunostained skeletal myofibers were foundthroughout the infracted areas and border zones, and the density of blood capillary in the MI region transplanted by myoblasts with VEGF,6s was increased （measured 4 weeks later and compared with controls）. Heart function was examined by the Buxco system and demonstrated that maximum dp/dt [（1607.23±102.67） mmHg/s vs （1217.77±89.91） mmHg/s] and minimum dp/dt [（-1535.09±81.34） mmHg/s vs （1174.58±91.5） mmHg/sJ were improved in the heart transplanted with the transfected myoblasts（P〈0.05）. Conclusion： Autologous skeletal myoblasts transfected with VEGF165 could ameliorate the blood supply in the MI region, and aid recovery of heart function more quickly in post-infarction hearts. This suggests an effective treatment for myocardium infarction.

关 键 词：VEGF165 成肌细胞 细胞移植 心肌梗死 

分 类 号：R542.22[医药卫生—心血管疾病]