[1]任 陈,李旋子,杜莎莎.维生素E通过抑制铁坏死减少放射性神经损伤[J].南方医科大学学报,2020,(08):1097-1102.
 Vitamin E reduces radiation injury of hippocampal neurons in mice by inhibitingferroptosis[J].Journal of Southern Medical University,2020,(08):1097-1102.
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维生素E通过抑制铁坏死减少放射性神经损伤()
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《南方医科大学学报》[ISSN:1673-4254/CN:44-1627/R]

卷:
期数:
2020年08期
页码:
1097-1102
栏目:
出版日期:
2020-07-30

文章信息/Info

Title:
Vitamin E reduces radiation injury of hippocampal neurons in mice by inhibiting ferroptosis
作者:
任 陈李旋子杜莎莎
关键词:
维生素E铁坏死放射损伤海马神经元
Keywords:
vitamin E ferroptosis radiation injury hippocampal neurons
文献标志码:
A
摘要:
目的 背景 探索维生素E在海马神经元放射性损伤过程中的作用并探讨其可能机制。方法 HT-22细胞及U251细胞体外培养,分别设置对照组:细胞正常培养;单纯放疗组(RT):放射线单次照射8 Gy;VE组:维生素E(200 μmol/L)处理24 h;Fer-1 组:铁坏死抑制剂(Ferrostatin-1,5 μmol/L)处理24 h;RT+VE组:放疗联合维生素E处理;RT+Fer-1组:放疗联合铁坏死抑制剂处理;RT + ZVAD 组:放疗联合凋亡抑制剂(ZVAD-FMK, 2 μmol/L)处理;RT + Necro-1 组:放疗联合坏死性凋亡抑制剂(nerosulfonamide, 100 μmol/L)处理。MTT实验测定各组细胞生长情况。检测铁坏死相关氧化应激指标包括还原型谷胱甘肽(GSH)、丙二醛(MDA)、脂质活性氧簇(Lipid ROS)以及细胞内铁离子水平评估各组细胞铁坏死状态。实验小鼠根据随机数表法随机分为4组(3只/组):对照组:小鼠正常喂养;VE组:维生素E(500 U/kg)饮食喂养6周;RT组:小鼠全脑单次16 Gy照射;RT+VE组:放疗联合维生素E处理。观察各组小鼠水迷宫实验的探索时间及探索距离评估小鼠认知功能状况。结果 与RT组相比,RT+VE组HT-22细胞存活增加(P<0.05),U251无明显改变(P>0.05);RT+Fer-1组HT-22细胞存活也明显增加(P<0.05),RT+ZVAD组和RT+Nerco-1组HT-22细胞存活无改变(P>0.05)。与对照组相比,RT组HT-22细胞铁坏死相关氧化应激水平上 升,包括GSH下降、MDA及Lipid ROS水平上升,细胞内铁离子水平增加(P<0.05);而与RT组相比,RT+VE组及RT+Fer-1组能逆转铁坏死相关氧化应激水平改变(P<0.05)。与对照组及VE组比较,RT组小鼠水迷宫实验中游行的距离和探索时间较RT组明显增加(P<0.05);RT+VE组小鼠相比于RT组水迷宫探索距离及时间均有明显下降(P<0.05)。结论 铁坏死,而非凋亡和坏死性凋亡,是海马神经元放射性损伤过程中的重要因素,维生素E能通过抑制铁坏死减少放射性神经损伤。
Abstract:
Objective To explore the protective effect of vitamin E (VE) against radiation injury of hippocampal neurons in mice and explore the possible mechanism. Methods Cultured HT-22 and U251 cells with or without exposure to 8 Gy irradiation were treated with VE (200 μmol/L for 24 h), ferroptosis inhibitor (ferrostatin-1, 5 μmol/L for 24 h), apoptosis inhibitor (ZVAD-FMK, 2 μmol/L), or necroptosis inhibitor (100 μmol/L). MTT assay was used to evaluate the cell viability after the treatments, and reduced glutathione (GSH), malondialdehyde (MDA), lipid reactive oxygen species (lipid ROS), and intracellular iron ion levels were detected for assessment of ferroptosis. The mice exposed to 16 Gy irradiation with or without vitamin E (500 U/kg) treatment for 6 weeks were assessed for behavioral changes and cognitive functions using Morris water maze test. Results Treatment with VE significantly promoted the cell survival following irradiation in HT-22 cells (P<0.05) but not in U251 cells (P>0.05). Ferrostatin-1, but not ZVAD or the necroptosis inhibitor, promoted the survival of HT-22 cells following the irradiation. Exposure to irradiation significantly increased ferroptosis-related oxidative stress level in HT-22 cells, manifested by decreased GSH level and increased MDA, lipid ROS and intracellular iron ion levels (P<0.05); treatment with VE and ferrostatin-1 both obviously reversed radiation-induced ferroptosis-related oxidative stress in the cells (P<0.05). In Morris water maze test, the mice with radiation exposure showed obviously increased exploration time and distance (P<0.05), which were significantly decreased after treatment with VE (P<0.05). Conclusion Vitamin E reduces radiation injury by inhibiting ferroptosis in the hippocampal neurons in mice.
更新日期/Last Update: 2020-07-29