血管内皮生长因子对猪心肌侧枝血管生成的作用  

Therapeutic angiogenesis with the use of vascular endothelial growth factor 165 gene in the myocardium of miniature swine

作　　者：张端珍[1] 盖鲁粤[1] 陈以旺 范瑞云[1] 文应峰[1] 董蔚[1] 

机构地区：[1]解放军总医院心内科,北京100853 [2]Section of Cardiology Veterans Affairs Medical Center

出　　处：《生理学报》2001年第3期183-187,共5页Acta Physiologica Sinica

摘　　要：为检测血管内皮生长因子１６５（ＶＥＧＦ１６５）能否促进冠状动脉侧枝血管形成，实验在成功制作小型猪慢性心肌缺血模型后，将以复制缺陷重组腺病毒为载体的人ＶＥＧＦ１６５互补脱氧核糖核酸［（ｃＤＮＡ）Ａｄ－ＶＥＧＦ１６５］直接注入左回旋支（ＬＣＸ）分布的缺血心肌内，以心电图门控单光子发射计算机断层摄影和离体冠状动脉造影检测冠状动脉侧枝形成、心肌灌注和功能变化。结果显示，与对照组和自身给予Ａｄ－ＶＥＧＦ１６５前比较，给予Ａｄ－ＶＥＧＦ１６５四周后心肌缺血面积（Ｐ＜０．０１）和最大缺血程度（Ｐ＜０．０１）明显减小，左心室射血分数（Ｐ＜０．０１）和ＬＣＸ区局部心室壁运动（Ｐ＜０．０５）明显改善，治疗组侧枝血管生成明显多于对照组（Ｐ＜０．０５），表明Ａｄ－ＶＥＧＦ１６５能诱导心肌侧枝血管形成并改善心肌灌注与运动功能。The purpose of the present study was to examine whether adenovirus-mediated vascular endothe-lial growth factor 165 (VEGF165) can enhance collateral vessel formation of coronary artery and improve re-gional myocardial perfusion and function. Using a miniature swine model of chronic myocardial ischemia, the replication-deficient recombinant adenovirus vector containing complementary deoxyribonucleic acid (cDNA) for human VEGF165 (Ad-VEGF165) or for β-galactosidase (Ad-Gal) was administered directly into the is-chemic myocardium in the left circumflex (LCX) distribution. Myocardial perfusion and function were assessed by electrocardiogram-gated single photon emission computed tomography (SPECT) imaging and collateral vessel development of coronary artery was assessed by ex vivo coronary angiography (CAG). Four weeks after AdVEGF165 administration, SPECT imaging demonstrated a significant reduction in ischemic area (P <0.01) and ischemic severity (P <0.01), and a substantial improvement in left ventricular ejection fraction (P < 0.01) and regional wall motion in the LCX distribution (P <0.05), as compared with that of control animals and that before administration of Ad-VEGF165. Collateral vessel development with Rentrop Grading was also significantly greater in Ad-VEGF165 animals than in the Ad-Gal control animals (P <0.05). It's concluded that Ad-VEGF165 can induce collateral vessel development in ischemic myocardium and result in significant improvement in myocardial perfusion and function.

关 键 词：内皮生长因子 基因治疗 缺血性心脏病 血管生成 心肌功能 侧枝循环 

分 类 号：R541.05[医药卫生—心血管疾病]