急性心肌梗死模型大鼠经血管内皮生长因子121基因治疗后的血管新生☆

背景：血管内皮生长因子121可能是基因治疗急性心肌梗死的合适目的基因之一。 目的：观察直接心肌注射重组腺病毒人血管内皮生长因子121基因(Ad-hVEGF121)对心肌梗死大鼠心脏结构、功能及新生血管影响。 方法：将78只SD大鼠随机分为假手术组(n=18)、心肌梗死组(n=24)、Ad-hVEGF121组(n=19)和生理盐水组(n=17)，后3组大鼠经结扎左冠状动脉前降支，建立急性心肌梗死模型。Ad-hVEGF121组和生理盐水组结扎后10~15 min分别在心肌三点注射Ad-hVEGF12和生理盐水。假手术组只开胸，不结扎左冠状动脉前降支。 结果与结论：注射后2周治疗组行心脏超声检查，发现相比于假手术组，心肌梗死组、Ad-hVEGF121组和生理盐水组大鼠心肌新生毛细血管数量、体质量和左心室质量/体质量明显增加(P < 0.05或P < 0.01)，且转染rAd-VEGF基因后心肌组织毛细血管密度显著高于生理盐水组和心肌梗死组。但4组大鼠的梗死面积、心脏结构和功能接近。提示直接心肌注射Ad-VEGF121能明显促进心肌内新血管形成。

Angiogenesis in acute myocardial infarction rats after vascular endothelial growth factor 121 gene therapy

BACKGROUND: Previous studies suggest that vascular endothelial growth factor 121 may be an optimal target gene for the treatment of acute myocardial infarction. OBJECTIVE: To investigate effect of direct myocardial injection of adenovirus recombinant human vascular endothelial growth factor 121 gene (Ad-hVEGF121) on myocardial infracted rat heart structure, function and angiogenesis. METHODS: Totally 78 male SD rats were randomly divided into the sham-surgery (n=18), acute myocardial infarction (n=24), Ad-VEGF121 (n=19) and normal saline (n=17) groups. Among them, left anterior descending coronary arteries of the latter three groups were ligated to prepare acute myocardial infarction models and rats were randomly selected to receive Ad-hVEGF12 or normal saline via three points in the cardiac muscle at the 10-15 minutes after ligation. The chest was exposed without ligation in the sham-surgery group.  RESULTS AND CONCLUSION: At 2 weeks after injection, cardiac ultrasound showed that, compared with the sham-surgery group, the number of new capillaries, body weight and left ventricular mass / body weight of the acute myocardial infarction, Ad-hVEGF121 and normal saline groups were obviously increased (P < 0.05 or P < 0.01), especially those received transfected rAd-hVEGF12, had higher density of blood capillaries than those of the normal saline and acute myocardial infarction groups. However, there were no obviously differences between each group in infarct size, cardiac structure or functions. The direct myocardial injection of Ad-VEGF121 can significantly promote the formation of new blood vessels within the myocardium.