为深入研究脉冲电场对细胞的作用机制,并进一步推广其在临床上的应用,基于有限元仿真软件建立了考虑胞内细胞器的单细胞五层介电模型,从2维和3维的角度研究分析了脉冲电场诱导细胞发生电穿孔的动态过程。同时,鉴于理论球形细胞与真实细胞结构的差异,建立不规则细胞介电模型,讨论分析脉冲电场作用于理论球形细胞与真实细胞电穿孔效应的差异。仿真结果表明:在1.5 k V/cm、10μs脉冲电场作用下,细胞膜上跨膜电位升高达到穿孔跨膜电位阈值(1 V)后发生穿孔,孔密度急增(达到1016数量级),电导率随着时间快速增加,从而进一步改变跨膜电位的分布,穿孔区域由正对电极的点逐渐往四周扩展,最终穿孔区域达到整个表面积的71.4%。而不规则细胞下的跨膜电位、电导率等分布较复杂,不再具有对称分布性,对于畸形度较大的细胞则必须考虑其形状的影响。仿真结果合理解释了脉冲作用下单细胞电穿孔的作用机制,为进一步分析复杂细胞系统提供理论依据,同时推进了脉冲电场的临床应用。
In order to understand the interaction mechanism between pulsed electric field and cells in-depth and further promote its applications in clinic, considering the intracellular organelles, the five-shelled dielectric model of spherical cell was established based on finite elements to simulate and analyze the dynamic processes of electroporation induced by pulse electric field from the aspect of two-dimension and three-dimension. Given the differences in cell structure between the ideal spherical cell and the real cell, the irregularly cell model was established to discuss the differences in electropo- ration effect between the ideal spherical cell and the real cell exposed in pulsed electric field. The results show that,under the electric field with the amplitude of the 1.5 kV/cm duration of 10 ~ts, the electroporation occurs with the rapid increase of the membrane conductivity and pore density (up to the stage of 1016) in the regions on the membrane where the trans- membrane potential is higher than the threshold (I V). The sharp increase of the membrane conductivity will modify the distribution of the transmembrane potential, leading to the expanding of the electroporated domain from the points face the electrodes to the place all around and making the whole regions of electroporation up to 71.4% of the superficial area of spherical cell. As to irregular cells, the distribution of transmembrane voltage and membrane conductivity is more complicated and asymmetrical. In present study, the results can explain the mechanism of electroporation reasonably, which provide a theoretical basis for further researching complicated cell systems and promoting the clinical application of pulsed electric field.