鼻咽癌细胞凋亡性容积减小的数学模型研究

项目名称： 鼻咽癌细胞凋亡性容积减小的数学模型研究

项目编号： No.30870567

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 金属学与金属工艺

项目作者： 陈丽新

作者单位： 暨南大学

项目金额： 32万元

中文摘要： 凋亡早期的细胞容积缩小（apoptotic volume decrease ，AVD）是凋亡过程的一个关键环节，氯通道及钾通道的激活是已知的凋亡过程事件中最早发生的变化。然而，我们对凋亡全过程中由多通道活动而产生的多种离子运动和它们对AVD和凋亡的综合影响还知之甚少。本研究主要采用最新发展的非损伤微测技术，结合膜片钳、细胞图像、计算机等技术，探讨了鼻咽癌细胞凋亡过程多种离子流与细胞容积、细胞凋亡的关系，构建了离子－凋亡性细胞容积缩小－凋亡的数学模型，发现凋亡诱导剂引起Cl-、K+、 H+ 离子跨膜转运活动发生变化，诱导AVD，在凋亡过程中这些离子跨膜转运规律不相同，而且它们对AVD和凋亡的重要性排序也不一样。氯通道的激活在AVD和凋亡中起着关键作用，Cl- 流可预测细胞容积的变化以及细胞凋亡的发生概率，而钾通道主要在激发AVD的早期起作用。P2嘌呤受体信号途径参与了凋亡早期氯通道的激活。本项目的完成有助于从离子流、AVD的角度揭示凋亡发生、发展规律，为研发离子通道介导的新型抗肿瘤药物提供了重要的实验依据。

中文关键词： 细胞凋亡；离子通道；非损伤微测技术；膜片钳技术；数学模型

英文摘要： The apoptotic volume decrease (AVD) in the early stage is a key process for cell apoptosis. The activation of Cl- and K+ channels is the earliest change of various activities observed during the apoptotic process. However, the dynamic time courses of various ion flows initiated by activation of various ion channels and the roles of different ion flows in AVD and apoptosis are still a puzzle that remains to be solved. In this study, the relationships between different ion flows, AVD and apoptosis were investigated, and the mathematic models expressing these relationships were established using the new-developed non-invasive ion-selective microelectrode technique, and the techniques of patch-clamping, imaging analysis and computation. It was found that apoptotic inducers initiated dynamic changes of the transmembrane fluxes of Cl-, K+ and H+, resulting in the occurrence of AVD in nasopharyngeal carcinoma cells. However, the activation and the dynamic time courses of different ion flows were differential during the apoptotic process, and the roles and importance of these ion flows in AVD and apoptosis were different. The activation of Cl- channels played a key role in AVD and in regulation of apoptosis induced by different drugs. Cl- flux may be a good index for predicting cell volume changes and the possibility of apoptosis. K+ channels mainly played their roles in the initiation of AVD in the early stage. The P2 purinoceptor signaling pathway was involved in the activation of Cl- channels in the early stage of apoptosis. The findings obtained from this study may benefit the uncovering of the underlying mechanism of apoptosis and facilitate the development of novel channel-targeting anti-tumor drugs.

英文关键词： Apoptosis; Ion Channels; Non-invasive Ion-selective Microelectrode Techniques; Patch-clamp Techniques; Mathematic Models