载uPA超声微泡递药体系的建立及其在室间隔缺损精准无创治疗中的可行性研究

室间隔缺损（VSD）是最常见的先天性心脏病之一，促进其自然愈合是最安全、无创及经济的治疗方法，其中室隔瘤样组织(ATVMS)的形成是PMVSD自然愈合的关键因素。本课题组前期研究结果表明尿激酶型纤溶酶原激活物（uPA）在ATVMS形成中发挥重要作用，然而uPA全身给药副作用大，并且局部药物浓度低。为临床安全有效应用uPA促进VSD愈合，我们将构建ADRB1-靶向载uPA超声微泡，并探索在心脏定点位置通过超声激发爆破微泡，从而在室缺周围形成局部高浓度uPA，促进室隔瘤形成，进而促进室缺愈合。本课题将在前期工作基础上，对靶向微泡的构建、超声激发的最优条件，维持局部高浓度的可靠性及安全性方面进行研究。本研究有望在促进VSD愈合方面开发出一种无创、安全的治疗新方法。

Ventricular septal defect (VSD) is the most common type of congenital heart disease, promoting the spontaneous closure of defect is a new non-invasive and economical treatment of VSD, which mostly due to the development of aneurysmal tissue of the ventricular membranous septum (ATVMS). Our previously results showed that Urokinase-type plasminogen activator (uPA) have a crucial role in the formation of ATVMS. Due to the concentration of uPA is not enough to work in cardiomyocytes by intravenous injection with large adverse effects, it limits its clinical use. In order to promote the closure of VSD, we will construct the microbubbles carried with uPA and ADRB1 which used to increase the concentration of uPA in the cardiomyocytes around defects by ultrasound-targeted microbubble destruction. In this study, in order to increase the concentration in cardiomyocytes and eliminate the adverse effects of uPA, we will systematically investigate the constructing of the microbubbles carried with uPA and ADRB1, as well as the best condition of ultrasound-targeted microbubble destruction. This study may provide a new non-invasive and economical treatment of ventricular septal defect.