血管内皮生长因子对小型猪心肌血管生成作用的研究

The therapeutic angiogenesis with the use of vascular endothelial growth factors gene in the myocardium of miniature swine

目的 :检测血管内皮生长因子 16 5 (VEGF16 5 )能否促进冠状动脉侧枝血管形成并改善心肌局部灌注与功能。方法 :小型猪做成慢性心肌缺血模型后 ,将以腺病毒为载体的重组人VEGF16 5互补脱氧核糖核酸 [(cDNA)Ad VEGF16 5 ]或 β 半乳糖酶cDNA直接注入冠状动脉回旋支分布的心肌内 ,以心电图门控单光子发射计算机断层摄影术 (SPECT)和离体心脏冠状动脉造影 (CAG)检测冠状动脉侧枝生成、心肌灌注及功能变化。结果 :与对照组和自身用药前SPECT检查相比 ,Ad VEGF16 5治疗后心肌缺血面积 (P <0 0 1)和最大缺血程度 (P <0 0 1)明显减小、左心室射血分数 (P <0 0 1)和LCX区局部室壁运动 (P <0 0 5 )明显改善 ,离体心脏CAG采用Rentrop分级示治疗组侧枝血管生成明显多于对照组 (P <0 0 5 )。结论 :Ad VEGF16

Objective:To evaluate the effect of vascular endothelial growth factor 165(VEGF165) on enhancing collateral vessel formation of the coronary artery(CA) and improving regional perfusion and function of the heart Methods:On a miniature swine model of chronic myocardial ischemia,adenovirus vector expressing recombinant human VEGF165 complementary deoxyribonucleic acid[( cDNA)Ad VEGF165] or expressing β galactosidasecDNA(Ad gal)was administered directly into the myocardium in the left circumflex(LCX)distribution Myocardial perfusion and function were assessed by ECG gated single photon emission computed tomography (SPECT) imaging and collateral vessel development ofCA was assessed by ex vivo coronary angiography(CAG) Results:SPECT imaging 4 weeks after Ad VEGF165 administration demonstrated significant reduction in ischemic area( P <0 01) and rest ischemic severity( P <0 01)and significant improvement in left ventricular ejection fraction( P <0 01) and the regional wall motion in the LCXdistribution ( P <0 05) compared with that of control animals and that before administration of Ad VEGF165 Collateral vessel development by CAG with Rentrop Grading was also significantly greater in Ad VEGF165 animals than in the Ad gal control animals( P <0 05) Conclusion:Ad VEGF165 induces collateral vessel development in ischemic myocardium and results in significant improvement in myocardial perfusion as well as function