摘要
目的探讨铁死亡抑制蛋白1(FSP1)对蛛网膜下腔出血(SAH)后神经元的保护作用。方法使用血红蛋白刺激细胞模拟SAH环境。使用过表达慢病毒上调FSP1,在细胞实验中分为对照组、血红蛋白组、血红蛋白+慢病毒组三组比较检测细胞铁死亡状况,检测指标包括:丙二醛水平、活性氧水平、细胞Fe2+水平,通过对照组、血红蛋白组、血红蛋白+iFSP1刺激组三组比较检测下调FSP1后细胞铁死亡状况。在细胞实验中分为对照组、血红蛋白组、血红蛋白+CoQ10刺激组检测补充CoQ10(FSP1底物)对细胞铁死亡的影响,在动物实验中分为假手术组、SAH组、SAH+CoQ10组检测CoQ10对小鼠的神经保护作用。结果慢病毒上调FSP1可以降低细胞丙二醛、活性氧及Fe2+水平(P<0.05)。iFSP1下调FSP1升高细胞丙二醛、活性氧及Fe^(2+)水平(P<0.05)。CoQ10可以上调细胞FSP1含量,降低细胞丙二醛、活性氧及Fe2+水平(P<0.05)。在动物实验中,CoQ10同样上调FSP1水平(P<0.05)。结论FSP1可以在SAH后抑制神经元铁死亡,是一个有效的干预靶点。
Objective To investigate the protective effect of ferroptosis suppressor protein 1(FSP1)on neurons after sub‐arachnoid hemorrhage(SAH),and aiming to find new intervention targets and therapeutic ideas for SAH.Methods The cells were stimulated by hemoglobin to simulate the SAH environment.Overexpressed lentivirus was used to up-regulate FSP1,and the cell exper‐iment was divided into control group,hemoglobin group,and hemoglobin+lentivirus group to compare and detect the status of ferropto‐sis in cells.The detection indexes included:the levels of malondialdehyde,reactive oxygen species and Fe2+were compared with the control group,hemoglobin group and hemoglobin+iFSP1 stimulation group to detect the ferroptosis status of cells after downregulating FSP1.In the cell experiment,they were divided into control group,hemoglobin group and hemoglobin+CoQ10 stimulation group to de‐tect the effect of CoQ10 supplementation(FSP1 substrate)on cell ferroptosis.In the animal experiment,they were divided into sham operation group,SAH group and SAH+CoQ10 group to detect the neuroprotective effect of CoQ10 on mice.Results Lentivirus up-regulation of FSP1 could decrease the levels of malondialdehyde,reactive oxygen species and Fe2+(P<0.05).The iFSP1 down-regulat‐ed FSP1 increased the levels of malondialdehyde,reactive oxygen species and Fe2+(P<0.05).CoQ10 could up-regulate the content of FSP1 and decrease the levels of malondialdehyde,reactive oxygen species and Fe^(2+)(P<0.05).In animal experiments,CoQ10 also up-regulated FSP1 level(P<0.05).Conclusion FSP1 can inhibit neuronal ferroptosis after SAH,which is an effective intervention tar‐get.
作者
彭铮
庞骢
李晓健
鲁悦
庄宗
李伟
杭春华
PENG Zheng;PANG Cong;LI Xiaojian;LU Yue;ZHUANG Zong;LI Wei;HANG Chunhua(Department of Neurosurgery,Nanjing Drum Tower Hospital,Affiliated Hospital of Medical School,Nanjing Universi-ty,Nanjing 210008,Jiangsu,China)
出处
《医学研究与战创伤救治》
CAS
北大核心
2024年第8期790-797,共8页
Journal of Medical Research & Combat Trauma Care
基金
国家自然科学基金(82371325)。
关键词
蛛网膜下腔出血
铁死亡
铁死亡抑制蛋白1
subarachnoid hemorrhage
ferroptosis
ferrop‐tosis suppressor protein 1
作者简介
通信作者:杭春华,E-mail:hang1965@nju.edu.cn。
