VEGF165和Ang-1协同改善急性心梗大鼠心功能

目的探讨血管内皮细胞生长因子和促血管生成素联合使用治疗大鼠急性心肌梗死及其机制.方法扩增携带人VEGF165或Ang-1的复制缺陷型病毒;制作大鼠急性心肌梗死模型,结扎后立即于缺血的心肌区域注射Ad-VEGF165或/和Ad-Ang-1,术后注射Brdu;免疫组织化学双染色观察新生内皮细胞和心肌细胞数;用超声心动图仪检测左心功能.结果VEGF165和Ang-1联合使用可显著改善左心功能.梗死区发现新生心肌细胞,并且新生的内皮细胞和心肌细胞数显著多于其他组,梗死区细胞表达C-kit阳性.结论VEGF165和Ang-1可显著改善急性心肌梗死大鼠心功能,其机制与骨髓造血干细胞的动员密切联系.

VEGF165 and angiopoietin-1synergistically improve cardiac function of the infarct rats

Objective This study was designed to evaluate the effects and mechanisms of VEGF165 and angiopoietins-1 (Ang-1) on therapy of the infarcted rats. Methods Replication-deficient adenovirus encoding for human VEGF_ 165 or angiopoietin-1 was amplified. Myocardial ischemia was induced in male rats by ligation of the left anterior descending (LAD) coronary artery. Ad5-VEGF165 or Ad5-Ang-1 or Ad5-GFP at 108PFU was injected into the ischemic myocardium immediately following LAD ligation. Brdu (50 mg/kg) was administered 1 week after ligation. At the second and fourth week, the hearts were harvested and sectioned for immunohistochemistry examination. Anti-factor VIII, anti-actin and anti-myosin heavy chain(MHC) were employed to stain endothelial cells(ECs), smooth muscle cells (SMCs) and cardiac myocytes(CMS). Numbers of Brdu (+) cells were counted at four different fields on each slide. M-mode echocardiography was used to evaluate the cardiac function at the first and fourth week. Results VEGF_ 165 and Ang1 significantly increased number of Brdu (+) endothelial cells (ECs) and cardiac myocytes(CMS) compared to control. VEGF and Ang1 also significantly improve the cardiac function. Conclusion The results suggest that the combination of VEGF and Ang1 gene therapy can improve the cardiac function of infarcted rats. Mobilization of marrow stem cell possibly play important role in this mechanism.