高压纳秒脉冲电场对同源细胞的杀伤差异性研究  

Study on the Killing Difference of Homologous Cells by High-Voltage Nanosecond Pulsed Electric Fields

作　　者：彭文成 唐潇 刘红梅[1] 董守龙[1] 姚陈果[1] Peng Wencheng;Tang Xiao;Liu Hongmei;Dong Shoulong;Yao Chenguo(State Key Laboratory of Power Transmission Equipment&System Security and New Technology Chongqing University,Chongqing 400044,China;State Grid Zhejiang Electric Power Company Hangzhou Power Supply Company,Hangzhou 310016,China)

机构地区：[1]输配电装备及系统安全与新技术国家重点实验室(重庆大学),重庆400044 [2]国网浙江省电力有限公司杭州供电公司,杭州310016

出　　处：《电工技术学报》2024年第20期6544-6552,共9页Transactions of China Electrotechnical Society

基　　金：国家自然科学基金(52237010);中央高校基本科研业务费医工融合专项(2023CDJYGRH-ZD04)资助项目。

摘　　要：为深入研究高压纳秒脉冲电场诱导同源细胞的生物电学效应的差异性,该文以人永生化角质形成细胞(HaCaT)、人黑色素瘤细胞(A375)和人黑色素瘤耐药细胞(A375/R)为研究对象,开展细胞悬液杀伤实验,并搭建肿瘤三维水凝胶模拟组织消融实验平台,分析高压纳秒脉冲电场对悬浮细胞的杀伤效应以及对模拟组织的消融效果。同时,结合单细胞真实几何尺寸建立有限元仿真模型,分析高压纳秒脉冲电场作用下几何尺寸对细胞核膜上穿孔面积以及穿孔数量的影响。实验结果显示,在高压纳秒脉冲作用下,正常细胞的存活率最高且消融面积最小,肿瘤耐药细胞的存活率最低且消融面积最大。实验与仿真结果表明,正常细胞、肿瘤细胞及肿瘤耐药细胞对高压纳秒脉冲电场的敏感性存在显著差异,高压纳秒脉冲电场对正常细胞的效果最弱,对肿瘤耐药细胞的效果最强。研究表明,高压纳秒脉冲电场在肿瘤消融领域具有不影响周边正常组织的潜在的临床应用价值。In terms of biological effects caused by the pulsed electric fields,the duration of the nanosecond pulse is less than the charging time constant of the cell membrane(~1μs),which has more profound effects on the intracellular organelles,known as the intracellular electron-manipulation.Based on this,the nanosecond pulsed electric fields(nsPEFs)have unique bioelectromagnetic properties in the field of tumor ablation.Therefore,the killing effects of homologous cells under the action of nsPEFs are studied to investigate the difference between homologous cells and high-voltage nsPEFs.The homologous cells,human immortal keratinocytes(HaCaT),human melanoma cells(A375),and human melanoma chemoresistant cells(A375/R)are chosen as research objects.The homemade pulse generator can output high-voltage nanosecond pulses with flexible and adjustable parameters.The selected pulse parameters are 5 kV/cm to 15 kV/cm field intensity,300 ns pulse width,1 Hz repetition frequency,and 80 pulse number.Cell viability assay based on CCK-8 is used to study the survival rate of homologous cells after pulse treatment.The ablation effect of nanosecond pulses is further studied based on hydrogel-simulated tissue.The lethal threshold for a specific ablation area is calculated.Furthermore,the electroporation response of the single cell to the nanosecond pulse is simulated by the finite element simulation model.The survival rate of the three cells decreases with the increase of the electric field intensity of nsPEFs.The cell viability assay shows that with the same nsPEFs parameters,the survival rate of normal cells is the highest,followed by tumor cells,and tumor chemoresistant cells have the lowest survival rate.The results of the hydrogel simulated tissue ablation experiment show that with the same pulse parameters,the ablation area of tumor chemoresistant cells is the largest,reaching(20.28±0.85)mm^(2),and the ablation area of normal cells is the smallest,only(10.26±0.49)mm^(2).Meanwhile,the lethal threshold of normal and chemoresistant ce

关 键 词：纳秒脉冲电场 同源细胞 细胞存活率 水凝胶模拟组织 杀伤差异性 

分 类 号：TM836[电气工程—高电压与绝缘技术] Q64[生物学—生物物理学]