前庭神经鞘膜瘤源性外泌体诱导HEI-OC1细胞铁死亡的研究

Study on vestibular Schwannoma-derived exosomes inducing ferroptosis in HEI-OC1 cells

迪丽胡玛尔·买买提明;高跃文;王朝晖;火子榕;杨涛;张治华

1:上海交通大学医学院附属第九人民医院耳鼻咽喉头颈外科

2:上海交通大学医学院耳科学研究所

3:上海市耳鼻疾病转化医学重点实验室

摘要
目的 探讨前庭神经鞘膜瘤(vestibular schwannoma, VS)来源外泌体(extracellular vesicles, EVs)对HEI-OC1细胞的损伤机制及铁死亡抑制剂铁抑制素-1(ferrostatin-1,Fer-1)对其的保护作用。方法 收集4例Ⅱ、Ⅲ期、听力分级为D级的VS患者的肿瘤组织及相关临床资料,提取VS原代细胞并收集其培养上清液。采用超速离心法提取VS外泌体(VS-EVs)并鉴定。体外培养HEI-OC1细胞,分为3组:空白对照组(不做任何处理)、EVs组(3 000颗粒/细胞VS-EVs处理24 h)、以及EVs+Fer-1组(20μmol/L Fer-1预处理2 h后与3 000颗粒/细胞VS-EVs共培养24 h)。利用CCK-8法检测各组细胞活性,DCFH-DA荧光探针定量检测活性氧(reactive oxygen species, ROS)水平,BODIPY 581/591 C11探针评估脂质过氧化水平。结果 与空白对照组相比,EVs组HEI-OC1细胞活性显著降低(P<0.001),ROS(P<0.001)和脂质过氧化物(P<0.001)水平升高;与Evs组相比,EVs+Fer-1组细胞活性有效恢复(P<0.001),ROS和脂质过氧化水平(P<0.001)降低。结论 VS-EVs通过破坏氧化还原稳态,促进细胞内脂质过氧化物和ROS积累,诱导HEI-OC1细胞铁死亡;Fer-1能够显著减轻VS-EVs引起的铁死亡,从而保护HEI-OC1细胞。
关键词
前庭神经鞘膜瘤;外泌体;铁死亡;HEI-OC1细胞
基金项目(Foundation):
国家自然科学基金面上项目(81870712);; 交大医学院地高大双百人项目(20191913)
作者
迪丽胡玛尔·买买提明;高跃文;王朝晖;火子榕;杨涛;张治华
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