钠钙交换体在动脉导管保持开放机制中的作用研究

项目名称： 钠钙交换体在动脉导管保持开放机制中的作用研究

项目编号： No.81200128

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学一处

项目作者： 洪海筏

作者单位： 上海交通大学

项目金额： 23万元

中文摘要： 动脉导管（Ductus Arteriosus，DA）在胚胎期保持开放，出生后关闭，是围产期心血管循环的关键环节。而对于30%左右的复杂先天性心脏病，DA保持开放又是出生后生命得以维持的"桥梁"。如果DA提前关闭，新生儿期急诊手术通常不可避免，明显降低手术成功率。前列环素可以保持DA一定程度的开放，但副作用率高达50%，因此临床迫切需要更好的药物去保持DA开放。钠钙交换体（Na+/Ca2+ Exchanger, NCX）是血管收缩舒张调节机制中最重要的环节之一，我们在前期工作中发现NCX在胚胎期DA保持开放机制中发挥了关键性的作用。本研究通过新生儿复杂先天性心脏病保持开放和收缩关闭的DA之间NCX在DA收缩舒张功能中的作用、表达和活性功能状态的差异以及调控NCX表达对DA收缩舒张功能影响的研究，全面的探讨NCX在动脉导管保持开放机制中的作用，以期为保持DA开放寻找新的潜在治疗靶点。

中文关键词： 动脉导管；钠钙交换体；钙离子；先天性心脏病；

英文摘要： The ductus arteriosus (DA), a structure that connects the pulmonary artery to the aorta in utero, plays a vital role in the fetal circulation. It is widely patent and shunts more than half of the deoxygenated cardiac output into the descending aorta. Postnatal patent DA plays an essential and constructive role as a 'bridge' for life-saving corrective surgery in one third of neonates with complicated congenital heart defects. If DA contricts in these patients, emergent operation is unavoidable. The DA can be maintained patent by E-type prostaglandins . However, treatment with a low dose of E-type prostaglandins causes complications in more than 50% of patients. Therefore, it is of great clinical relevance to identify the mechanism by which the DA remains patent. The Sodium-calcium Exchanger(NCX) is a major regulator of Vasoconstriction and Vasodilation. In our preliminary study, we found that hypoxia-induced dilation in fetal DA results from cytosolic calcium efflux mediated primarily by the forward mode of NCX. In this study, we examine the expression of NCX, the active state of NCX, the NCX's effect on vasoconstriction and vasodilation as well as it's modulation in DA between patency and closure for comprehensive understanding NCX's effect on patency of DA and looking for the new potential therapeutic target t

英文关键词： ductus arteriosus；Sodium-calcium Exchanger；concentration；congenital heart disease；