Ferrostatin-1通过抑制Ferroptosis保护谷氨酸诱导的HT-22细胞损伤

发布时间：2018-01-24 12:03

  本文关键词： 谷氨酸 HT- Ferroptosis Ferrostatin- 神经保护　出处：《中国临床药理学与治疗学》2016年10期 　论文类型：期刊论文

【摘要】：目的:观察谷氨酸诱导HT-22细胞发生Ferroptosis的现象,以及初步探讨Ferrostatin-1对谷氨酸损伤的HT-22细胞保护作用机制。方法:建立谷氨酸损伤HT-22细胞研究模型,并采用MTT检测细胞存活率,同时观察3-Methyladenine、Z-VAD-FMK、Necrostatin-1、Ferrostatin-1对细胞存活率的影响;乳酸脱氢酶(LDH)释放法检测乳酸脱氢酶的漏出率;流式细胞术检测细胞内活性氧(ROS)的含量变化;生化法检测超氧化物歧化酶(SOD)、谷胱甘肽(GSH)变化。结果:5mmol/L谷氨酸作用HT-22细胞24 h后,能明显抑制细胞生长(P0.01);增加细胞LDH的释放;ROS含量增加;SOD活性下降;GSH水平下降。Ferrostatin-1预处理后,谷氨酸诱导的HT-22细胞存活率显著增加(P0.01),而3-Methyladenine、Z-VAD-FMK、Necrostatin-1不能显著阻止谷氨酸对HT-22细胞的生长抑制作用;同时,Ferrostatin-1能够阻止谷氨酸引起的细胞内LDH释放,减少ROS生成;SOD活性增加;促进GSH水平增加。结论:谷氨酸损伤的HT-22细胞可以被Ferroptosis特异性抑制剂Ferrostatin-1阻断,不能被其他死亡抑制剂阻断,表明谷氨酸诱导的HT-22细胞发生了Ferroptosis。谷氨酸通过引起ROS升高,降低细胞内GSH水平、SOD活性诱导HT-22细胞发生Ferroptosis。Ferrostatin-1对谷氨酸损伤的HT-22细胞具有保护作用,其作用机制与抗氧化的发生有关。
[Abstract]:Objective: to observe the occurrence of Ferroptosis in HT-22 cells induced by glutamate. To explore the protective mechanism of Ferrostatin-1 on HT-22 cells injured by glutamate. Methods: to establish the model of HT-22 cells injured by glutamate. MTT was used to detect cell viability and 3-Methyladenine Z-VAD-FMKN Necrostatin-1 was observed at the same time. The effect of Ferrostatin-1 on cell survival; Lactate dehydrogenase release assay was used to detect the leakage rate of lactate dehydrogenase. The content of reactive oxygen species (Ros) in cells was detected by flow cytometry. The changes of superoxide dismutase (SOD) and glutathione (GSH) were detected by biochemical method. Results HT-22 cells were treated with 5 mmol / L Glutamic acid for 24 h. The cell growth was inhibited significantly (P 0.01). The release of LDH was increased. ROS content increased; The activity of SOD decreased. The survival rate of HT-22 cells induced by glutamate increased significantly (P 0.01) after GSH level decreased. Ferrostatin-1 was pretreated with Glutamic acid. However, 3-Methyladenine Z-VAD-FMKN Necrostatin-1 did not significantly inhibit the growth inhibition of HT-22 cells by glutamate. At the same time, Ferrostatin-1 could prevent glutamate induced LDH release and reduce ROS production. SOD activity increased; Conclusion: glutamate damaged HT-22 cells can be blocked by Ferroptosis specific inhibitor Ferrostatin-1. It could not be blocked by other death inhibitors, suggesting that glutamate induced HT-22 cells had reduced GSH levels by increasing ROS levels. SOD activity induces Ferroptosis.Ferrostatin-1 in HT-22 cells to protect Glutamic acid damaged HT-22 cells. Its mechanism is related to the occurrence of antioxidation.
【作者单位】： 安徽中医药大学科研实验中心;安徽中医药大学新安医学教育部重点实验室;
【分类号】：R741
【正文快照】： 刘晨旭,女,硕士,研究方向:分子药理学。Tel:0551-65169371 E-mail:xuxu3688@sina.com神经退行性疾病是神经细胞出现渐进性的功能异常而导致的机体行为异常和功能障碍的常见病,主要包括阿尔茨海默病、帕金森病等[1]。在神经退行性疾病的众多病因学说中,兴奋性氨基酸毒性是国内，

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