质膜去极化在声空化介导细胞凋亡中的作用机理研究

项目名称： 质膜去极化在声空化介导细胞凋亡中的作用机理研究

项目编号： No.81201098

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 影像医学与生物医学工程

项目作者： 秦鹏

作者单位： 上海交通大学

项目金额： 23万元

中文摘要： 低强度超声联合微泡的声空化效应能够介导细胞凋亡为临床肿瘤治疗提供了又一选择。其无创、可靶向聚焦以及低成本的独特优点彰显了这一物理疗法的优势。在超声，微泡和细胞相互作用中，质膜作为细胞最外层的保护屏障，直接接受声空化的能量刺激，其电生理状态的变化-去极化在开启细胞内部凋亡通路中起着重要的作用。本研究在对声空化效应进行实时测量的基础上，以体外癌细胞系为模型，通过分析声空化效应剂量、质膜去极化和细胞内单价阳离子浓度的变化、质膜上相关离子通道蛋白及载体蛋白活性之间的相关关系，以揭示这些离子和膜蛋白同声空化效应介导的外源性及内源性线粒体凋亡途径之间的信号传导关系。通过该项研究，期望深入理解质膜去极化在在声空化介导细胞凋亡中的作用机理，发现能对声空化效应迅速响应的靶向蛋白，提出改进声空化介导细胞凋亡效率的策略，为声空化走向临床肿瘤治疗提供充分、可靠的理论基础。

中文关键词： 声空化；微泡；质膜；去极化；凋亡

英文摘要： The interaction between the low intensity ultrasound pulses and microbubbles is known to generat acoustic cavitation that may mediate cell apoptosis,which offers an effective approach for clinical tumor treatment.Noninvasion，focusing on the targeted objective and low cost are the advantages of this physical treatment of disorders. When the combined use of the low intensity ultrasound and microbubbles is exposed to the cell, acoustic cavitation will firstly give rise to the change of the electrophysiological status of plasma membrane, which is the outmost protective barrier of the cell. It is no doubt that plasma membrane depolarization plays the important role in triggering the intracellular apoptotic pathways. In this research, based on the establishment of the ultrasound exposure setup and the real-time measurement of acoustic cavitation, the in vitro cancer cell line is adopted to ananlyze the interraction among the acoustic cavitation dosage, plasma membrane depolarization and intracellular cations, ion channels and plama membrane ATPase transporter, and reveal the signal conduction from the changes of these intracellular cations and membrna proteins to the intrinsic and extrinsic apoptotic pathways induced by acoustic cavitation. We expect to achieve a more complete understanding of the role of the plasma

英文关键词： Acoustic Cavitation；Microbubbles；Plasma Membrane；Depolarization；Apotosis