纳秒脉冲电场通过破坏线粒体诱导心肌消融研究  

Nanosecond Pulsed Electric Fields Induce Myocardial Ablation by Destroying Mitochondria

作　　者：吴胜军 陈若诗 陈新华[2,3] 滕鹏 马量 WU Shengjun;CHEN Ruoshi;CHEN Xinhua;TENG Peng;MA Liang(Division of Cardiovascular Surgery,Zhejiang University School of Medicine,Hangzhou Zhejiang 310003,China;Division of Hepatobiliary and Pancreatic Surgery,The First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou Zhejiang 310003,China;Zhejiang Provincial Key Laboratory of Pulsed Power Translational Medicine,Hangzhou Zhejiang 311100,China)

机构地区：[1]浙江大学附属第一医院心脏大血管外科,浙江杭州310003 [2]浙江大学附属第一医院肝胆胰外科,浙江杭州310003 [3]浙江省脉冲电场技术医学转化重点实验室,浙江杭州311100

出　　处：《中国医疗设备》2023年第5期25-30,共6页China Medical Devices

基　　金：国家自然科学基金(82070516)。

摘　　要：目的通过纳秒脉冲电场(Nanosecond Pulsed Electric Field,nsPEF)对体内外心肌细胞的实验研究,探讨其对细胞凋亡及对心脏活动的影响,并通过转录组研究进一步探讨机制。方法利用0~20 kV/cm场强对体外H9c2心肌细胞进行各50次电击的消融试验,确定能实现有效细胞凋亡的参数,进一步在此参数下进行小鼠心肌消融及转录组研究。结果15 kV/cm场强+50次电击体外心肌细胞在0、24、48 h的凋亡率分别为62.3%、78.8%、80.6%,可见消融区域线粒体膜结构明显破坏,诱导心肌细胞进入凋亡调控,导致心肌细胞释放细胞色素c;小鼠心肌完全消融率达76.2%。结论15 kV/cm场强+50次电击通过破坏线粒体诱导心肌凋亡并最终实现消融区域心肌细胞坏死性凋亡,且不影响心脏周围的其他组织,可作为心房颤动(Atrial Fibrillation,AF)消融的有效手段。Objective The effect of nanosecond pulsed electric field(nsPEF)on cardiomyocytes apoptosis and cardiac activity was investigated in vitro and in vivo,and the mechanism was further explored by transcriptome study.Methods H9c2 cardiomyocytes were ablated by 50 times of electric shock at 0-20 kV/cm field intensity to determine the parameters that could achieve effective cell apoptosis.Then,mouse cardiomyocytes were ablated under these parameters and transcriptomic studies were conducted.Results The apoptosis rates of cardiomyocytes at 0 h,24 h and 48 h were 62.3%,78.8%and 80.6%,respectively,at 15 kV/cm field intensity plus 50 shocks.The mitochondrial membrane structure in the ablation area was obviously damaged,and the cardiomyocytes were induced to enter apoptosis regulation,leading to the release of cytochrome c.The total ablation rate of mouse myocardium was 76.2%.Conclusion 15 kV/cm field intensity+50 shocks can induce myocardial apoptosis by destroying mitochondria and eventually achieve necrotic apoptosis of myocardial cells in ablation area without affecting other tissues around the heart,which can be used as an effective means for ablation of atrial fibrillation.

关 键 词：纳秒脉冲电场 心肌细胞 心房颤动 线粒体 凋亡 

分 类 号：R541.7[医药卫生—心血管疾病] R312[医药卫生—内科学]