Efficacy and safety of therapeutic angiogenesis from direct myocardial administration of an adenoviral vector expressing vascular endothelial growth factor 165  

腺病毒介导的血管内皮生长因子 1 6 5诱导猪心肌血管生成和安全性研究(英文)

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

机构地区：[1]北京市解放军总医院心内科,北京100853

出　　处：《Chinese Medical Journal》2002年第5期643-648,145,共6页中华医学杂志（英文版）

摘　　要：OBJECTIVE: To investigate whether direct administration of adenoviral vectors (Ad) containing the complementary deoxyribonucleic acid (cDNA) of vascular endothelial growth factor 165 (Ad-VEGF165) induces porcine coronary collateral vessel formation, improves regional myocardial perfusion and function and is safe. METHODS: Three weeks after miniature swine underwent left thoracotomy and placement of an Ameroid constrictor on the left circumflex coronary artery (LCX), Ad-VEGF165 (n = 6) or the control, Ad expressing beta-galactosidase cDNA (Ad-Gal, n = 6), was directly administered into the ischemic myocardium in the circumflex distribution. All animals were sacrificed 4 wk after the second surgery. Myocardial perfusion and function were assessed by electrocardiogram-gated single photon emission computed tomography (GSPECT) imaging. Ex vivo coronary angiography was performed to examine collateral vessels. Toxicity was assessed by blood analyses on the day just before (day 0) and on day 1, 3, 7, 28 after vector delivery and by vascular, myocardial and liver histology after sacrifice. RESULTS: GSPECT imaging 4 wk after administration of Ad-VEGF165 demonstrated significant reduction in ischemic area (P目的　探讨以腺病毒 (Ad)为载体的血管内皮生长因子 16 5cDNA(Ad VEGF16 5 )能否诱导猪缺血心肌血管生成、改善心肌灌注和功能并是否安全。方法　将小型猪行胸廓切开术后将Ameroidconstrictor置于左冠状动脉回旋支近端。 3周后随机分成两组 ,再次行胸廓切开术并将Ad VEGF16 5 (n =6 )或对照剂以Ad为载体的β 半乳糖酶基因 (Ad Gal,n =6 )注入LCX分布区的缺血心肌内 ,喂养 4周。以心电图门控单光子发射计算机断层显像检测心肌灌注和功能 ,以离体冠状动脉造影检测侧枝血管生成。于载体释放前 (第 0天 )和释放后第 1、3、7、2 8天抽血行血常规、肝肾功能、心肌酶检测并行血管、心肌、肝脏组织学检查以检测其安全性。结果　与对照组和治疗组注射Ad VEGF16 5之前相比 ,给予Ad VEGF16 5治疗 4周后心肌缺血面积 (P <0 0 1)、静息最大缺血程度 (P <0 0 1)明显减小 ,左心室射血分数 (P <0 0 1)和局部室壁运动 (P <0 0 5 )明显改善。冠状动脉造影示治疗组侧枝血管明显多于对照组 (P <0 0 5 )。对照组和治疗组血常规、肝肾功能和心肌酶检测示仅第2 8天时红细胞计数和血尿素氮略有差别 (P <0 0 5 ) ,与载体释放前比较 ,两组均仅在第 1天的肌酸磷酸激酶 (P <0 0 5 )和谷丙转氨酶 (P <0 0 5 )有短暂升高。

关 键 词：ADENOVIRIDAE Animals Collateral Circulation Coronary Angiography Coronary Vessels DNA  Complementary Electrocardiography Endothelial Growth Factors Female Gene Therapy Gene Transfer Techniques Genetic Vectors LYMPHOKINES Male Myocardial Ischemia Neovascularization  Physiologic SWINE Swine  Miniature Tomography  Emission-Computed  Single-Photon Treatment Outcome Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors 

分 类 号：R540.2[医药卫生—心血管疾病]