本文關(guān)鍵詞： 谷氨酸 HT- Ferroptosis Ferrostatin- 神經(jīng)保護(hù)　出處：《中國臨床藥理學(xué)與治療學(xué)》2016年10期 　論文類型：期刊論文

【摘要】：目的:觀察谷氨酸誘導(dǎo)HT-22細(xì)胞發(fā)生Ferroptosis的現(xiàn)象,以及初步探討Ferrostatin-1對谷氨酸損傷的HT-22細(xì)胞保護(hù)作用機(jī)制。方法:建立谷氨酸損傷HT-22細(xì)胞研究模型,并采用MTT檢測細(xì)胞存活率,同時觀察3-Methyladenine、Z-VAD-FMK、Necrostatin-1、Ferrostatin-1對細(xì)胞存活率的影響;乳酸脫氫酶(LDH)釋放法檢測乳酸脫氫酶的漏出率;流式細(xì)胞術(shù)檢測細(xì)胞內(nèi)活性氧(ROS)的含量變化;生化法檢測超氧化物歧化酶(SOD)、谷胱甘肽(GSH)變化。結(jié)果:5mmol/L谷氨酸作用HT-22細(xì)胞24 h后,能明顯抑制細(xì)胞生長(P0.01);增加細(xì)胞LDH的釋放;ROS含量增加;SOD活性下降;GSH水平下降。Ferrostatin-1預(yù)處理后,谷氨酸誘導(dǎo)的HT-22細(xì)胞存活率顯著增加(P0.01),而3-Methyladenine、Z-VAD-FMK、Necrostatin-1不能顯著阻止谷氨酸對HT-22細(xì)胞的生長抑制作用;同時,Ferrostatin-1能夠阻止谷氨酸引起的細(xì)胞內(nèi)LDH釋放,減少ROS生成;SOD活性增加;促進(jìn)GSH水平增加。結(jié)論:谷氨酸損傷的HT-22細(xì)胞可以被Ferroptosis特異性抑制劑Ferrostatin-1阻斷,不能被其他死亡抑制劑阻斷,表明谷氨酸誘導(dǎo)的HT-22細(xì)胞發(fā)生了Ferroptosis。谷氨酸通過引起ROS升高,降低細(xì)胞內(nèi)GSH水平、SOD活性誘導(dǎo)HT-22細(xì)胞發(fā)生Ferroptosis。Ferrostatin-1對谷氨酸損傷的HT-22細(xì)胞具有保護(hù)作用,其作用機(jī)制與抗氧化的發(fā)生有關(guān)。
[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.
【作者單位】： 安徽中醫(yī)藥大學(xué)科研實(shí)驗(yàn)中心;安徽中醫(yī)藥大學(xué)新安醫(yī)學(xué)教育部重點(diǎn)實(shí)驗(yàn)室;
【分類號】：R741
【正文快照】： 劉晨旭,女,碩士,研究方向:分子藥理學(xué)。Tel:0551-65169371 E-mail:xuxu3688@sina.com神經(jīng)退行性疾病是神經(jīng)細(xì)胞出現(xiàn)漸進(jìn)性的功能異常而導(dǎo)致的機(jī)體行為異常和功能障礙的常見病,主要包括阿爾茨海默病、帕金森病等[1]。在神經(jīng)退行性疾病的眾多病因?qū)W說中,興奮性氨基酸毒性是國內(nèi)，

本文編號：1460006