纳秒脉冲作用下核孔复合体影响细胞核膜电穿孔变化的仿真研究  

Simulation Study on the Effect of Nuclear Pore Complexes on Cell Electroporation Under Nanosecond Pulse

作　　者：程显[1,2] 陈硕 吕彦鹏[1,2] 葛国伟 连昊宇 Cheng Xian;Chen Shuo;Lü Yanpeng;Ge Guowei;Lian Haoyu(School of Electrical Engineering,Zhengzhou University,Zhengzhou,450001,China;Henan Engineering Research Center of Power Transmission&Distribution Equipment and Electrical Insulation,Zhengzhou,450001,China)

机构地区：[1]郑州大学电气工程学院,郑州450001 [2]河南省输配电装备与电气绝缘工程研究中心,郑州450001

出　　处：《电工技术学报》2021年第18期3821-3828,共8页Transactions of China Electrotechnical Society

基　　金：国家自然科学基金青年项目(52007172);中国博士后面上项目(2020M672273);河南省重点研发与推广专项(科技攻关)项目(212102310247)资助。

摘　　要：纳秒脉冲电场能够透过细胞膜,靶向作用到细胞核膜产生电穿孔,从而诱导细胞死亡。而细胞核膜上存在的大量具有高电导率的核孔复合体(NPC)将会制约细胞核膜上电穿孔的发展。然而,现有纳秒脉冲电穿孔的仿真研究中尚未考虑此因素的影响。基于此,该文建立考虑细胞核上NPC存在的五层细胞介电模型,在细胞核膜不同区域等距离设置8个核孔进行仿真研究。通过COMSOL软件的电流模块和偏微分计算分析模块,首次研究NPC对细胞核电穿孔程度的影响。结果表明,与无核孔时的细胞核电穿孔状态相比,NPC的存在会导致附近一定区域内的核膜上电穿孔程度显著性下降,甚至会转变为未电穿孔状态,NPC附近核膜电穿孔衰减程度也与NPC的位置相关;随着NPC数量的增加(2~32个),细胞核膜上电穿孔明显衰减的区域也逐渐增加,当NPC个数达到32个时,细胞核膜上电穿孔程度发生衰减的区域百分比已达到89.93%,衰减50%以上的区域百分比为36.00%,衰减90%以上的区域百分比可达到22.94%,而因NPC存在导致周围区域由穿孔状态变为未穿孔状态的百分比也达到2.54%。上述研究表明,NPC的存在会极大地降低周围细胞核电穿孔效应及整体细胞核电穿孔的程度,从而显著影响纳秒脉冲杀伤肿瘤细胞的效果。因此,在对靶向诱导细胞核膜电穿孔的纳秒脉冲电场参数选择时,应考虑NPC的影响。The nanosecond pulsed electric field(nsPEF)can penetrate the cell membrane and target the nuclear membrane to produce electroporation,thereby inducing cell death.However,the existence of a lot of nuclear pore complexes(NPCs)with high conductivity on the nuclear membrane will restrict the development of nuclear electroporation,but it has not been considered in the simulation of nanosecond pulse electroporation.Therefore,in this paper,a five-layer cell dielectric model with NPC in the nucleus was established,and eight NPCs were set at equal distances in different regions of the nuclear membrane.The effect of NPC on nuclear electroporation was studied through the current module and partial differential module of COMSOL.The results showed that:compared with the nuclear membrane electroporation without NPC,the presence of NPC significantly attenuated nuclear membrane electroporation and even changed to a non-electroporation state,and the attenuation degree of nuclear membrane electroporation near NPC was also related to the position of NPC.With the increase in the number of NPC(2~32),the areas with marked attenuation of electroporation on the nuclear membrane also gradually increased.When the number of NPC reached 32,the percentage of areas with attenuation electroporation on the nuclear membrane was 89.93%,the percentages of areas with 50% and 90% attenuation electroporation were 36.00% and 22.94% respectively,and the percentage of areas from electroporation to none-electroporation due to the presence of NPC was 2.54%.In conclusion,NPC can greatly reduce the electroporation on the nuclear membrane,thereby significantly affecting the effect of the nsPEF ablating tumor cells.Therefore,the effect of NPC should be considered when determining the parameters of the nsPEF for the electroporation of nuclear membrane.

关 键 词：有限元 电穿孔 核孔复合体 介电模型 跨膜电位 孔密度 

分 类 号：TM151[电气工程—电工理论与新技术]