脉冲电场作用下细胞跨膜电压变化的机理研究

发布时间：2018-05-05 10:44

本文选题：电疗法 + 跨膜电压　；参考：《重庆大学》2005年硕士论文

【摘要】：癌症是威胁人类生命的主要疾病之一。传统的治疗方法由于受到其适应症、禁忌症和副作用等限制,它们对恶性肿瘤的治疗效果仍不够理想。电疗法(包括电穿孔疗法、细胞内电处理疗法和陡脉冲疗法)是近三十年发展起来的治疗恶性肿瘤的新技术,对人体深部和浅表肿瘤的杀伤效应强,且可以有效控制杀伤范围,在肿瘤的局部治疗中已展现出广阔的应用前景。虽然各种电疗法的机理各有不同,但它们都是基于外加脉冲电场所诱导的跨膜电压超过细胞膜或细胞核膜的击穿电压临界值,造成膜的可逆或不可逆性击穿,从而实现单独或辅助治疗癌症的目的。本文在分析细胞的生理物理特性及介电物理特性的基础上,基于经典的球形单细胞三层介电模型,考虑细胞核等细胞器的影响,提出了更为合理、更接近实际情况的球形单细胞五层介电模型。根据五层介电模型推导得出了稳恒电场作用下细胞跨膜电压的解析式,并给出了时变场作用下跨膜电压的求解方法。通过计算仿真理想方波脉冲电场作用下细胞的跨膜电压发现:随着脉宽减小,跨细胞膜电压和跨核膜电压都随之减小,但跨核膜电压与跨细胞膜电压的比值随脉宽的减小而增加,定量地证明了脉冲越窄对细胞核的作用越强,揭示了极窄脉冲诱导细胞凋亡的可能性。通过计算仿真计及上升沿的实际指数衰减脉冲电场作用下的细胞跨膜电压和跨核膜电压发现:脉冲的上升时间常数τr 越小,细胞跨膜电压越大,但是当τr 小到一定程度后,再减小τr ,对细胞跨膜电压的影响不再明显;而指数衰减脉冲的下降时间常数则对跨膜电压的数值起决定性作用。最后,本文在深入分析正常组织和肿瘤组织的电特性的基础上,建立了肿瘤组织物理模型,并借助FEMLAB 数值分析软件对最为常用的两针电极和本课题组研制的七针电极在组织中的电场分布进行了仿真。通过对比分析两针电极与七针电极阵列的电场分布表明:七针电极阵列是合理的。
[Abstract]:Cancer is one of the major diseases threatening human life. Because of the limitation of indication, contraindication and side effect of traditional treatment, the effect of traditional treatment on malignant tumor is still not satisfactory. Electrotherapy (including electroporation, intracellular electrotherapy and steep pulse therapy) is a new technique for the treatment of malignant tumors developed in the last 30 years. It has strong killing effect on deep and superficial tumors of the human body and can effectively control the killing range. In the local treatment of tumor has shown a broad application prospects. Although the mechanisms of electrotherapy vary, they are based on the fact that the transmembrane voltage induced by an external pulse field exceeds the critical value of the breakdown voltage of the cell membrane or nuclear membrane, resulting in reversible or irreversible breakdown of the membrane, In order to achieve the purpose of treatment of cancer alone or auxiliary. On the basis of analyzing the physiological and physical properties and dielectric properties of cells, based on the classical three-layer dielectric model of spherical single cell and considering the influence of cell organelles such as nucleus, this paper puts forward a more reasonable method. A spherical single-cell five-layer dielectric model closer to the actual situation. According to the five-layer dielectric model, the analytical formula of cell transmembrane voltage under steady electric field is derived, and the solution method of transmembrane voltage under time-varying field is given. By simulating the cell transmembrane voltage under the action of an ideal square wave pulse electric field, it is found that with the decrease of pulse width, both the transmembrane voltage and the transnuclear membrane voltage decrease. However, the ratio of the transnuclear membrane voltage to the transmembrane voltage increased with the decrease of the pulse width. It was proved quantitatively that the narrower the pulse was, the stronger the nuclear effect was, and the possibility of apoptosis induced by the very narrow pulse was revealed. By calculating the cell transmembrane voltage and the transnuclear membrane voltage under the action of the actual exponential attenuation pulse electric field along the rising edge, it is found that the smaller the rising time constant 蟿 r, the greater the cell transmembrane voltage, but when 蟿 r is small to a certain extent, The effect of 蟿 r on the transmembrane voltage is not obvious, but the decreasing time constant of exponentially attenuated pulse plays a decisive role in the value of the transmembrane voltage. Finally, based on the deep analysis of the electrical properties of normal and tumor tissues, a physical model of tumor tissue is established. The electric field distribution of the most commonly used two needle electrodes and the seven needle electrodes developed by our team was simulated with the help of FEMLAB software. The electric field distribution of two needle electrode array and seven needle electrode array is analyzed, which shows that the seven needle electrode array is reasonable.
【学位授予单位】：重庆大学
【学位级别】：硕士
【学位授予年份】：2005
【分类号】：R35

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