【摘要】 目的　在体条件下探讨血管内皮生长因子16 5 (VEGF16 5 )和血管生成素 1(angiopoietin 1,Ang 1)对心脏缺血损伤的保护作用及其机制。 方法　构建编码人VEGF16 5 和Ang 全长基因的复制缺陷型腺病毒载体Ad VEGF16 5 和Ad Ang1。结扎SD大鼠冠状动脉前降支 ,在缺血区周围心肌内注射Ad VEGF16 5 和 (或 )Ad Ang1,术后 72h检测心脏组织中三磷酸肌醇激酶活性和抗凋亡因子Bcl 2表达水平 ;术后 1周收取心脏 ,分析结扎区内梗死心肌的面积变化。结果　Ang 1和VEGF16 5 单用组及两者联用组心肌梗死面积显著减小。其中 ,Ang 1单用组和两者联用组效果要好于VEGF16 5 单用组。VEGF16 5 和 (或 )Ang 1转染后 ,心肌内三磷酸肌醇激酶活性和Bcl 2表达水平均显著增高。结论VEGF16 5 和 (或 )Ang 1可激活心脏中三磷酸肌醇激酶并促进Bcl 2表达 ,减小心肌梗死面积 ,有明确的心脏保护作用更多还原

【Abstract】 Objective To investigate in vivo the possible heart protective effect and involved mechanisms of two angiogenic growth factors, vascular endothelial growth factor 165 (VEGF 165 ) and angiopoietin-1(Ang1) Methods Left anterior descending coronay arteries (LAD) were ligated in rats Replication-deficient adenovirus encoding for Ang1 (Ad-Ang1) or VEGF 165 (Ad-VEGF 165 ) was injected immediately into myocardium adjacent to ischemic region A replication-deficient adenovirus encoding for green fluorescent protein (Ad-GFP) was used as vehicle control Seventy-two hours later, rat hearts were harvested Phosphatidylinositol-3 kinase (PI-3K) activity and Bcl-2 expression in myocardium were investigated using immunoprecipitated kinase assay and Western blot assay respectively One week after gene transfection, rat hearts were harvested Myocardial infarct area was analyzed Results Myocardial infarct area was significantly decreased in Ad-VEGF 165 , Ad-Ang1, and Ad-Ang1+Ad-VEGF 165 treated groups as compared to Ad-GFP treated group (Ad-GFP vs Ad-VEGF 165 vs Ad-Ang1 vs Ad-Ang1+Ad-VEGF 165 :48 60% vs 29 96% vs 14 55% vs 9 54%, P<0 01) The infarct area was even smaller in Ad-Ang1 treated and Ad-Ang1+Ad-VEGF 165 treated groups as compared to Ad-VEGF 165 treated group(Ad-VEGF 165 vs Ad-Ang1 vs Ad-Ang1+Ad-VEGF 165 :29 96% vs 14 55% vs 9 54%, P<0 01) PI-3K activity increased in Ad-VEGF 165 , Ad-Ang1 and Ad-Ang1+Ad-VEGF 165 treated groups as compared to Ad-GFP treated group (Ad-GFP vs Ad-VEGF 165 vs Ad-Ang1 vs Ad-Ang1+Ad-VEGF 165 :4 11 vs 16 36 vs 24 43 vs 24 85, P<0 01) Bcl-2 (antiapoptosis factor)expression was up-regulated in Ad-Ang1 and Ad-Ang1+Ad-VEGF 165 treated groups as compared to Ad-GFP treated group (Ad-GFP vs Ad-Ang1 vs Ad-Ang1+Ad-VEGF 165 :2 63 vs 6 89 vs 6 25, P<0 01) Conclusion VEGF 165 and/or Ang1 decrease myocardial infarct size in rat LAD ligation model, which is related to the activation of PI-3 K signaling pathway and the up-regulation of Bcl-2 expression in heart The protective effects of VEGF 165 and Ang1 on ischemic myocardium broaden their functional research and would be potential for their clinical utilization including angiogenesis更多还原