载NaHS靶向微泡对糖尿病性海绵体内皮功能障碍的评估及修复作用

The pathogenesis of diabetes mellitus erectile dysfunction (DMED) depends on cavernous vascular endothelial dysfunction. Consequently, many studies focus on how to noninvasively evaluate endothelial function and improve the dysfunction. There is no ideal method yet, and the first-line drug's efficacy of these patients is poor. Targeted microbubbles are expected to solve the above problem, which are not only the molecular probes of ultrasound, but also effective carriers of drugs. This project is based on the principle of targeted contrast enhanced ultrasound and local drugs release by ultrasonic cavitation. Based on successful preparation of microbubbles targeted to endothelial cells, we are to build poly (lactic-co-glycolic acid, PLGA) microbubbles, which are targeted to E-selectin and containing NaHS. And this project is focused on solving: 1) noninvasive quantitative evaluation of the DMED cavernous vascular endothelial function using PLGA microbubbles targeted to E-selectin; 2)triggering the production of H2S gas after release of NaHS by ultrasonic cavitation of microbubbles, which is to induce penile erection and repair damaged endothelial-smooth muscle system of DMED. This project would provide a method of noninvasive assessment of vascular endothelial function and a technology of targeted delivery of therapeutic gas, which would develop and integrate the theory of pathogenesis and treatment of DMED.

糖尿病性勃起功能障碍（DMED）的核心发病机制为海绵体血管内皮功能障碍，其评估及改善治疗是DMED的研究热点。但目前尚无理想的内皮功能检测方法，且此类患者常用药物疗效较差。靶向微泡是超声分子探针，也是携带药物的有效载体，因此，有望解决上述问题。本项目基于靶向超声造影及局部空化微泡释药的原理，在前期成功制备靶向内皮细胞微泡的基础上，构建载NaHS靶向E选择素乳酸-羟基乙酸共聚物（PLGA）微泡，重点解决：1）靶向E选择素的PLGA微泡定量评估DMED海绵体血管内皮功能；2）超声空化微泡释放NaHS，触发H2S气体产生，诱发阴茎勃起，修复受损的DMED内皮-平滑肌系统。通过本研究，有望提供一种评估局部血管内皮功能状态的新方法及靶向输送治疗性气体的新技术，深化DMED的发病机制及治疗理论。

糖尿病性勃起功能障碍（DMED）的核心发病机制为海绵体血管内皮功能障碍，其评估及改善治疗是DMED的研究热点。本研究按照计划顺利完成，针对靶向功能显影内皮细胞及局部空化释放H2S改善内皮-平滑肌细胞功能的问题，项目构建了携带NaHS的纳米阳离子靶向造影剂，对微泡进行了基本特性表征、靶向能力检测、载药包封率测定及空化释药能力测定；同时利用构建的平行平板流动腔建立内皮细胞及平滑肌细胞体系，检测空化细胞损伤关系及内皮-平滑肌修复能力评估；在大鼠DMED模型上，验证其靶向造影能力，并评估对内皮-平滑肌细胞功能的影响。