circSLC8A1介导ATF3通路影响癫痫氧化应激及铁活性的机制  

circSLC8A1 mediates the mechanism of ATF3 pathway on oxidative stress and iron activity in epilepsy

作　　者：柴文[1] 谢琛 张骥[1] 邹冬琴[1] 方素素 康钦 CHAI Wen;XIE Chen;ZHANG Ji;ZOU Dongqin;FANG Susu;KANG Qin(Department of Neurology,Jiangxi Provincial People’s Hospital,the First Affiliated Hospital of Nanchang Medical College,Nanchang 330006,Jiangxi,China)

机构地区：[1]江西省人民医院/南昌医学院第一附属医院神经内科,江西南昌330006

出　　处：《中国现代医生》2025年第7期1-4,10,共5页China Modern Doctor

基　　金：江西省卫生健康委科技计划项目(202410128)。

摘　　要：目的分析circSLC8A1介导转录激活因子3(activating transcription factor 3,ATF3)通路影响癫痫细胞氧化应激及铁活性的机制。方法采用无Mg2+方法构建人神经元-海马细胞癫痫模型,检测健康对照组和模型组细胞的circSLC8A1、ATF3表达水平,采用质粒转染方式建立敲除circSLC8A1组、敲除ATF3组、敲除circSLC8A1+过表达ATF3组、敲除ATF3+过表达circSLC8A1组,转染6h后更换正常培养基培养48h。检测并比较不同干预组的细胞活力、铁活性、活性氧(reactive oxygen species,ROS)、乳酸脱氢酶(lactate dehydrogenase,LDH)和谷胱甘肽(glutathione,GSH)差异。结果模型组细胞的circSLC8A1、ATF3、ROS、LDH表达水平及铁活性均显著高于健康对照组,细胞活力和GSH表达水平均显著低于健康对照组(P<0.05);敲除circSLC8A1可显著降低癫痫模型细胞circSLC8A1表达量,敲除ATF3可显著降低癫痫模型细胞ATF3表达量(P<0.05);敲除circSLC8A1或ATF3,可使癫痫模型细胞的细胞活力升高,铁活性降低,氧化应激反应缓解,敲除circSLC8A1并过表达ATF3可逆转上述趋势,但敲除ATF3过表达circSLC8A1并不会导致上述现象。结论circSLC8A1能够通过介导ATF3通路,对癫痫模型对细胞活性、氧化应激反应及铁活性进程产生一定影响,可为癫痫产生机制及靶向治疗提供借鉴。Objective To analyze the effects of activating transcription factor 3(ATF3)pathway mediated by circSLC8A1 on oxidative stress and iron activity of epileptic cells.Methods An epileptic cell model was established using human neuronal-hippocampal cells through Mg2+-free method.The expression levels of circSLC8A1 and ATF3 in healthy control group and model group were detected.Plasmid transfection was used to establish circSLC8A1 knockout group,ATF3 knockout group,circSLC8A1 knockout+ATF3 overexpression group,and ATF3 knockout+circSLC8A1 overexpression group.After 6h transfection,cells were cultured in normal medium for 48h.The cell viability,iron activity,reactive oxygen species(ROS),lactate dehydrogenase(LDH)and glutathione(GSH)of the different intervention groups were detected and compared.Results The expression levels of circSLC8A1,ATF3,ROS,LDH and iron activity in model group were significantly higher than those in healthy control group,while cell activity and GSH expression were significantly lower than those in healthy control group(P<0.05).Knocking out circSLC8A1 can significantly reduce the expression of circSLC8A1 in epileptic model cells,while knocking out ATF3 can significantly reduce the expression of ATF3 in epileptic model cells(P<0.05).Knocking out circSLC8A1 or ATF3 will increase the cell viability,decrease the iron activity and relieve the oxidative stress in epileptic model cells.Knocking out circSLC8A1 and overexpressing ATF3 can reverse the above trend,but knocking out ATF3 and overexpressing circSLC8A1 will not lead to the above phenomenon.Conclusion circSLC8A1 can influence the cell activity,oxidative stress and iron activity process of epileptic model cells by mediating ATF3 pathway,which provides some reference for the mechanism of epilepsy and its targeted therapy.

关 键 词：circSLC8A1通路 ATF3通路 癫痫进程 氧化应激 铁活性 细胞活性 

分 类 号：R742.1[医药卫生—神经病学与精神病学]