协同脉冲增强不可逆电穿孔消融疗效的多参数效应分析及活体大动物实验研究  

Multi-parameter Effect Analysis and Large Living Animal Experimental Study of Synergistic Pulse-enhanced Irreversible Electroporation Ablation

作　　者：岳亚琪 董守龙[1] 马欣 彭文成 余亮 姚陈果[1] YUE Yaqi;DONG Shoulong;MA Xin;PENG Wencheng;YU Liang;YAO Chenguo(State Key Laboratory of Power Transmission Equipment&System Security and New Technology,Chongqing University,Chongqing 400030,China)

机构地区：[1]重庆大学输配电装备及系统安全与新技术国家重点实验室,重庆400030

出　　处：《高电压技术》2023年第12期5246-5259,共14页High Voltage Engineering

基　　金：国家自然科学基金(51807016,52237010);重庆市自然科学基金(cstc2020jcyj-msxmX0932);重庆市高等教育教学改革研究项目(213052)。

摘　　要：纳微秒协同的脉冲电场新型波形的提出为增强传统不可逆电穿孔消融疗效提供了重要的研究方向,然而目前对于新型的协同脉冲肿瘤消融技术,其在参数效应方面的研究还较为初步。为此以肝癌细胞系Hepa1–6为研究对象,从单细胞和2D模拟组织水平,结合细胞活性研究以及荧光分子探针技术测量消融范围,首次系统性分析协同脉冲各个参数(脉宽、电压、个数、频率和间隔时间)对肿瘤细胞消杀效应的影响规律(消融面积、活性率),提出能显著提高治疗效果的协同参数组合。结果表明,肿瘤细胞消杀效果与协同脉冲的纳秒脉宽(300~800 ns)、电压(纳秒脉冲:1.2~2 kV,微秒脉冲:200~400 V)和个数呈正相关,与频率(0.1~100 Hz)呈负相关,而间隔时间(1μs~1ms)影响不显著。在此基础上,首次开展临床前大动物试验,进一步验证了协同脉冲组织消融的可行性。该研究表明了协同脉冲可显著提高不可逆电穿孔消融疗效、建立了脉冲参数与疗效间的量效关系,同时也为新一代协同脉冲不可逆电穿孔肿瘤消融技术的临床应用提供了数据支撑、奠定了实验基础。The proposal of a new waveform of nano-microsecond synergistic pulsed electric field provides a promising research direction for enhancing the therapeutic efficacy of traditional irreversible electroporation ablation.However,the investigation of parameter effects in the new synergistic pulsed tumor ablation technology is still in its early stages.In this study,the Hepa1-6 liver cancer cell line was utilized as the research subject.From the level of individual cells and 2D simulated tissue,combining cell viability assessments and fluorescent molecular probe technology to measure the ablation range,we systematically analyzed the influences of various parameters of synergistic pulses(pulse width,voltage,number,frequency,and interval time)on tumor cell killing effects(ablation area and activity rate)for the first time.A synergistic parameter combination that significantly improved the therapeutic outcome was proposed.The results demonstrated that the inhibitory effect on tumor cells was positively correlated with nanosecond pulse width(300~800 ns),voltage(ns pulse:1.2~2 kV,μs pulse:200~400 V),and the number of synergistic pulses,while being negatively correlated with frequency(0.1~100 Hz).The effect of interval time(1μs~1 ms)was found to be insignificant.Based upon these findings,the first preclinical large animal test was conducted to further validate the feasibility of synergistic pulse tissue ablation.This re-search demonstrates that synergistic pulses can significantly enhance the therapeutic efficacy of irreversible electroporation ablation,and a dose-effect relationship between pulse parameters and treatment outcomes can be estab-lished.The results can provide essential data support and experimental groundwork for the clinical application of the next-generation synergistic pulse irreversible electroporation tumor ablation technology.

关 键 词：肿瘤治疗 不可逆电穿孔 协同脉冲 参数效应 临床前大动物试验 

分 类 号：R730.5[医药卫生—肿瘤]