直接心肌植入VEGF_(165)基因的实验研究

Experimental study on transmyocardial injection of plasmid DNA encoding the gene for vascular endothelial growth factor in the ischemic porcine heart

目的 :评估VEGF1 6 5基因直接心肌内注射促进心肌血运重建的疗效。方法 :中国实验小型猪 11只 ,体重 (2 9 3± 4 3)kg。在左冠状动脉回旋支 (LCX)近心端放置Ameroid收缩环。术后 6周行冠脉造影示LCX狭窄 >95 %为慢性心肌缺血模型形成。将选用模型随机分为治疗组 (n =6 )和对照组 (n =5 )。治疗组将VEGF1 6 5质粒注射到左室侧壁 10处有标记的心肌中层。对照组只注射空白质粒。治疗前和治疗 6周后 ,采用体表超声心动图观察静息与小剂量多巴酚丁胺负荷 (LDDSE)状态下左心室壁运动及功能 (LVEF、RT、MVCF、WMSI) ,通过2 0 1 TI SPECT观察心肌灌注改变。处死动物后进行心肌血管密度和VEGF基因mRNA表达测定。结果 :治疗 6周后 ,在静息与LDDSE(10 μg min kg)状态下 ,A组RT和WMSI较治疗前显著改善 ,侧壁灌注缺损明显缩小 ,B组改善不明显。A组每个视野的血管面积、血管周长及血管数目均较B组多。A组 2 3例局部心肌VEGF基因mRNA的表达明显 ,B组 3 3例均无表达。结论 :直接心肌内注射VEGF1 6 5基因可促进慢性缺血心肌的血管再生 ,改善局部心肌灌注和室壁运动。

Objective:To evaluate the efficiency of myocardial revascularization by Vascular Endothelial Growth factor (VEGF).Method:Chinese experimental swine underwent thoracotomy and placement of an Ameroid constrictor on the circumflex coronary artery. Six weeks later, coronary angiography was performed to show the block of circumflex artery, myocardial perfusion and function were assessed by 201 TI SPECT and by dobutamin echocardiography. An expression plasmid containing the gene\|encoding VEGF 165 (500 μg) and was administered directly into the myocardium at 10 sites in the circumflex distribution at group A( n =6), the empty plasmid vector was injected as the same mean at group B( n =5). Six weeks after injection, all studies were repeated and the capillary density or expression of VEGF mRNA of treated myocardium was measured.Result:The ischemic wall motion and perfusion of ischemic area was improved significantly, also the expression of VEGF mRNA of injected myocardium was detected in group A, but no any changes in group B. The capillary density myocardium increased statistically in Group A compared with the control. Conclusion:An expression plasmid containing the gene encoding VEGF 165 induces collateral vessel development in ischemic myocardium and results in significant improvement in both myocardium perfusion and function. [