超声斑点追踪技术评价微泡造影剂介导SERCA2a基因治疗心肌梗死大鼠的实验研究

Ultrasound-mediated destruction of microbubbles directs SERCA2a gene delivery to rats with myocardial infarction by two-dimensional ultrasound speckle tracking imaging

目的 应用二维超声斑点追踪显像技术评价超声微泡造影剂介导rAAV2-SERCA2a基因靶向治疗心肌梗死大鼠左心室功能的疗效.方法 健康雄性SD大鼠35只,随机分为3组：假手术组、心肌梗死组和基因治疗组.心肌梗死组及基因治疗组结扎冠状动脉左前降支近端,造成前壁心肌梗死.假手术组单纯开胸不结扎冠状动脉.4周时,基因治疗组注射rAAV2-SERCA2a与造影剂混合液,假手术组及心肌梗死组仅注射造影剂,以上各组均给予心肌定点超声辐照.干预4周时,测量各组大鼠左心室短轴观乳头肌水平径向应变率（radial strain rate,SRrad）和圆周应变率（circumferential strain rate,SRcir）的收缩期峰值（SRrad-S,SRcir-S）及舒张早期峰值（SRrad-E,SRcir-E）以及左室心肌扭转角度等.结果 干预4周时,基因治疗组各节段SRcir-S、SRcir-E、SRrad-S、SRrad-E以及左室扭转角度较心肌梗死组增加（P＜0.01）,与假手术组差异无统计学意义.结论 超声微泡造影剂介导rAAV2-SERCA2a基因转导至心肌组织,可有效改善心肌梗死大鼠左室心肌功能.

Objective To evaluate the therapeutic effects of rAAV2-SERCA2a gene targeted to myocardium by the ultrasound mediated microbubbles in rats with myocardial infarction（MI） using speckle tracking echocardiography （STE）. Methods Thirty-five male SD rats were divided into Sham group, MI group and gene therapy group. rAAV2-SERCA2a was attached to the surface of SonoVue, sulphur hexafluoride-filled microbubbles. Therapy group animals were infused with those mixed fluids through tail vein. The other two groups were infused with SonoVue microbubbles. These bubbles were infused with simultaneous echocardiography. Four weeks after ultrasound microbubbles destructed,Circumferential strain rate（SRcir）, radial strain rate（SRrad） and left ventricular torsion （LVtor） of regional myocardium were measured in short-axis view using speckle tracking imaging software for each animal. Results Compared with the M1 group,there were significant increase in SRcir-S,SRcir-E, SRrad-S,SRrad-E and LVtor in rats of gene therapy group（ P ＜0. 01 ）. There was no significant difference between gene therapy group and sham group. Conclusions rAAV2-SERCA2a gene targeted to myocardium by the ultrasound mediated microbubbles could enhance cardiac function of rats with MI.