超声引导下经胸穿刺心肌注射血管生成素1基因联合超声靶向破坏微泡治疗犬心肌梗死疗效及安全性评价  

The effect of ultrasound guided via chest puncture injection and ultrasound targeted microbubble destructionmediated the Angl gene therapy in myocardial infarction canines

作　　者：曹省[1] 周青[1] 陈金玲[1] 胡波[1] 胡伟[1] 崔晶晶[1] 单迎光[2] 郭瑞强[1] 

机构地区：[1]武汉大学人民医院超声影像科心血管病湖北省重点实验室,430060 [2]武汉大学人民医院心血管内科,430060

出　　处：《中华超声影像学杂志》2017年第8期713-718,共6页Chinese Journal of Ultrasonography

基　　金：国家自然科学基金资助项目（81471674,81501495）;中央高校基本科研业务费专项资金资助（2015301020203）

摘　　要：目的超声引导下经胸穿刺心肌注射血管生成素1（Ang1）基因联合超声靶向破坏微泡（UTMD）转染犬梗死心肌，评价其疗效及安全性。方法39只杂种犬随机平分为3组（每组13只）：①心肌梗死（心梗）组（心梗造模但未经治疗）；②静脉注射组（心梗造模后经静脉注射＋UTMD）；③心肌注射组（心梗造模后经胸超声引导下心肌注射＋UTMD）。4周后比较各组犬的存活率及常见并发症发生率；超声心动图测量左室内径和收缩功能；Masson染色评价梗死纤维化程度；免疫荧光CD31评估新生毛细血管密度；Western blotting检测Ang1蛋白表达量。结果①三组间存活率及并发症比较，差异无统计学意义（P〉0．05）；②与心梗组比较，静脉注射组左室收缩末期内径（LVESD）减小，左室射血分数（LVEF）增大，心肌注射组左室舒张末期内径（LVEDD）和LVESD均减小，LVEF增大（均P《0．05）；③心肌注射组较心梗组和静脉注射组纤维化程度减轻，新生毛细血管数量明显增多（P〈0．05）；④Ang1蛋白表达量在心肌注射组较心梗组和静脉注射组增加，差异均有统计学意义（P〈0．05）。结论超声引导下经胸心肌注射联合UTMD是一种安全、有效的基因转染方式，其介导Ang1转染可促进心肌血管新生，改善左室功能。Objective To evaluate the effect of ultrasound guided via chest puncture injection and ultrasound targeted microbubble destruction（UTMD）-mediated the angiogenin1 （Ang1） gene therapy in myocardial infarction （MI） canines. Methods Thirty-nine dogs were divided into three groups （each group 13 dogs）： （1） MI group （MI dogs without treatment）; （2）intravenous injection group （MI dogs with intravenous injection and UTMD treatment）; （3）myocardial injection group （MI clogs with myocardial injection and UTMD treatment）. Four weeks later, the safety and incidence of complications were compared. The dimensions and systolic function of left ventricular were measured by echocardiography. The percentage of collagen fiber was assessed by Masson. CD31 was applied for quantifying capillary density. The Angl protein was detected by Western blotting. Results （1）The survival and complications showed no significant difference among the 3 groups （all P 〉0.05）. （2）Compared with MI group, the left ventricular end-systolic dimension （LVESD）reduced and the left ventricular ejection fraction （LVEF） increased in intravenous injection group; the left ventricular end-diastolic dimension（LVEDD）and LVESD were both reduced in myocardial injection group, the LVEF was increased significantly（all P 〈0.05）. （3） The immunohistochemistry showed lower collagen fiber percentage and higher blood vessel density in myocardial injection group than those in the other groups（ P 〈0.05）. （4）The relative quantity of Angl was significantly higher in myocardial injection group than those of the other groups. The differences were statistically significant （ P 〈0.05）. Conclusions The combination of ultrasound guided via chest puncture injection and UTMD is a safe and effective method for gene transfection. It mediates Angl gene transfection that can promote angiogenesis after MI and improve left ventricular systolic function.

关 键 词：超声处理 心肌注射 基因转染 心肌梗死 

分 类 号：R445.1[医药卫生—影像医学与核医学] R542.22[医药卫生—诊断学]