超声造影剂介导血管内皮生长因子基因治疗心肌缺血的实验研究

目的探讨超声破坏造影剂微泡介导血管内皮生长因子(VEGF)基因转染兔缺血心肌的有效性。方法新西兰白兔48只，结扎兔冠状动脉左旋支，建立急性心肌梗死模型。术后3d，经胸超声检查左室壁运动情况，明确心肌缺血区域，然后将VEGF真核表达质粒与新型超声造影剂JD-95混合后，经耳缘静脉输入兔体内，同时进行超声实时造影成像，照射心脏缺血区。其他对照组包括超声和造影剂组、单独基因组、基因和超声组、基因和造影剂组以及空白对照组。术后17d处死动物，取动物缺血心肌、肝、肾及下肢骨骼肌组织，用免疫组化方法检测VEGF蛋白表达。结果在超声破坏造影剂微泡介导基因转染的实验组中5只兔的缺血心肌中VEGF蛋白的表达，2只兔肾有VEGF表达。而其他对照组中无VEGF蛋白表达。结论超声破坏造影剂微气泡的方法是将体外生物活性物质传递至心肌中的一种有效途径。

Ultrasound-mediated destruction of microbubbles directs gene delivery to ischemic myocardium of rabbits

Objective To investigate the feasibility of gene delivery to the ischemic myocardium of rabbits by ultrasound-mediated destruction of microbubbles. Methods A ligation model of left circumflex branch coronary artery was established in 48 rabbits. Three days after ligation, the mixture of gene and microbubbles was infused into the vein of rabbits with or without simultaneous ultrasound. Additional controls included ultrasound of microbubbles that did not contain gene, gene alone, gene plus ultrasound,and blank control. Rabbits were killed after two weeks and examined for the expression of vascular endothelial growth factor(VEGF). Results The hearts of five rabbits that underwent ultrasound-mediated destruction of microbubbles containing gene showed VEGF expression in ischemic myocardium.None of the control animals showed VEGF expression. Conclusions Ultrasound-mediated destruction of microbubbles is a promising method for the delivery of bioactive agents to the heart.