微泡产生过程的能量学和动力学以及微泡导致细胞损伤的关键因素研究

项目名称： 微泡产生过程的能量学和动力学以及微泡导致细胞损伤的关键因素研究

项目编号： No.11274046

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 数理科学和化学

项目作者： 涂展春

作者单位： 北京师范大学

项目金额： 78万元

中文摘要： 微泡是激活或凋亡细胞释放的一种亚微米尺度的脂质膜泡。在病理条件下，如在糖尿病和心血管疾病中，血浆中的微泡数量显著增加，微泡水平升高又反过来刺激其他正常细胞而导致损伤，加剧病情发展。尽管前期基础医学研究初步揭示了微泡的产生途径，但单纯医学实验无法使研究更深入。本项目试图从基本物理原理出发提出问题，并借助物理学的最新观测手段，结合基础医学实验深入探讨血管内皮细胞来源微泡的产生机理（包含微泡释放过程自由能的变化以及微泡数量与刺激信号强度的关系等），精确观测微泡形态和尺寸分布并定量阐明它们与微泡内容物的关系，初步探索微泡导致正常细胞损伤的机理（包含微泡内容物的关键作用、微泡导致细胞损伤的直接后果以及微泡与膜融合的自由能变化等）。该项目的完成将为今后确定微泡导致细胞损伤的完整途径提供线索，为研究糖尿病和心血管疾病的发病机制和临床诊断提供理论依据和新思路，为将物理学方法应用于医学研究提供范例。

中文关键词： 微泡；自由能；尺寸；损伤；形态

英文摘要： Microvesicles are lipid vesicles in submicrometer scales released from activated or apoptotic cells. In pathologic conditions such as diabetes mellitus and cardiovascular disease, the number of microvesicles in blood plasma is highly increased, which in return stimulates and induces injury to the other normal cells and hence aggravates the diseases quickly. Although the primary generation mechanism of microvesicles has been unveiled through the previous basic medical researches, the purely medical experiments can hardly go deeply. In this project the scientific questions as follows are proposed from the viewpoint of fundamental physical principles and will be solved with the aid of the latest physical equipments and the basic medical experiments: (i) the generation mechanism of endothelial microvesicles which includes the free energy changes during the blebbing and shedding of microvesicles as well as the relationship between the number of microvesicles and the strength of stimulating factors is fully investigated; (ii) the shapes and size distributions of microvesicles as well as the relationship between them and the contents of microvesicles are accurately measured and quantitatively interpreted; (iii) the mechanism for microvesicle-induced injury to normal cells which includes the key role that the content of

英文关键词： Microvesicle；free energy；size；injury；morphology