Shohet R V, Chen S, Zhou Y T, Wang Z, Meidell R S, Unger R H, Grayburn P A
Department of Internal Medicine, University of Texas Southwestern Medical Center and Veterans Administration Medical Center, Dallas, Tex, USA.
Circulation. 2000 Jun 6;101(22):2554-6. doi: 10.1161/01.cir.101.22.2554.
The noninvasive, tissue-specific delivery of therapeutic agents to the heart would be a valuable clinical tool. This study addressed the hypothesis that albumin-coated microbubbles could be used to effectively deliver an adenoviral transgene to rat myocardium by ultrasound-mediated microbubble destruction.
Recombinant adenovirus containing beta-galactosidase and driven by a constitutive promoter was attached to the surface of albumin-coated, perfluoropropane-filled microbubbles. These bubbles were infused into the jugular vein of rats with or without simultaneous echocardiography. Additional controls included ultrasound of microbubbles that did not contain virus, virus alone, and virus plus ultrasound. One group underwent ultrasound-mediated destruction of microbubbles followed by adenovirus infusion. Rats were killed after 4 days and examined for beta-galactosidase expression. The hearts of all rats that underwent ultrasound-mediated destruction of microbubbles containing virus showed nuclear staining with 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside substrate, indicating expression of the transgene. None of the control animals showed myocardial expression of the beta-galactosidase transgene. By quantitative analysis, beta-galactosidase activity was 10-fold higher in the treated group than in controls (P<0.0001).
Ultrasound-mediated destruction of albumin-coated microbubbles is a promising method for the delivery of bioactive agents to the heart.
将治疗药物无创、组织特异性地输送到心脏将是一种有价值的临床工具。本研究探讨了以下假设：白蛋白包被的微泡可通过超声介导的微泡破坏有效地将腺病毒转基因输送到大鼠心肌。
含有β-半乳糖苷酶并由组成型启动子驱动的重组腺病毒附着于白蛋白包被、充满全氟丙烷的微泡表面。这些微泡通过颈静脉注入大鼠体内，同时进行或不进行超声心动图检查。其他对照包括不含病毒的微泡超声、单独的病毒以及病毒加超声。一组先进行超声介导的微泡破坏，然后注入腺病毒。4天后处死大鼠并检查β-半乳糖苷酶的表达。所有接受含病毒微泡超声介导破坏的大鼠心脏，用5-溴-4-氯-3-吲哚基-β-D-吡喃半乳糖苷底物检测时均显示核染色，表明转基因表达。对照动物均未显示β-半乳糖苷酶转基因的心肌表达。通过定量分析，治疗组的β-半乳糖苷酶活性比对照组高10倍（P<0.0001）。
超声介导的白蛋白包被微泡破坏是一种将生物活性药物输送到心脏的有前景的方法。
