摘要
背景:LKB 1/AMPK信号通路作为代谢检查点参与了脑缺血损伤的发病机制。米诺环素,一种四环素衍生物,通过减少炎症、氧化应激和细胞凋亡,对脑缺血起到保护作用。本研究旨在探讨米诺环素对局灶性脑缺血损伤大鼠氧化标志物及LKB/AMPK信号通路的影响,阐明米诺环素对局灶性脑缺血损伤的神经保护机制。方法:将线插入左侧大脑中动脉,建立Wistar大鼠局灶性脑缺血损伤模型。2,3,5-三苯基四氮唑蓝(TTC)染色标记梗死体积.用生化法测定丙二醛(MDA)和过氧化脂质(LPO)的含量。所有其他项目均采用Westernblotting法测定。结果:米诺环素可降低脑梗死体积,但对神经功能评分无影响。米诺环素改善脑缺血再灌注大鼠海马GPX-1/2、GSS和GR的生物活性,限制GGT1的活性。米诺环素还能提高SOD的生物活性,对抗脂质过氧化。米诺环素可提高脑缺血再灌注大鼠海马LKB 1活性及3种AMPK亚基水平。结论:米诺环素通过调节抗氧化酶,激活LKB 1/AMPK信号通路,有效抑制急性脑梗死过程中的氧化应激。
关键词: 脑缺血,能量代谢,氧化应激,四环素,LKB 1/AMPK,米诺环素。
Current Molecular Medicine
Title:An Antioxidant Role by Minocycline Via Enhancing the Activation of LKB1/AMPK Signaling in the Process of Cerebral Ischemia Injury
Volume: 18 Issue: 3
关键词: 脑缺血,能量代谢,氧化应激,四环素,LKB 1/AMPK,米诺环素。
摘要: Background: LKB1/AMPK signaling pathway, as a metabolic checkpoint, is involved in the pathogenesis of cerebral ischemia injury. Minocycline, a tetracycline derivative, protects against cerebral ischemia via reducing inflammation, oxidative stress, and apoptosis. The aim of the study was to evaluate the influence of minocycline on oxidative biomarkers and LKB1/AMPK signaling pathway in Wistar rats with focal cerebral ischemia injury and to clarify the neuroprotective mechanism of minocycline against focal cerebral ischemia injury.
Methods: The focal cerebral ischemia injury of Wistar rats was established by inserting a thread into the left middle cerebral artery. 2,3,5-Triphenyltetrazolium chloride (TTC) staining was used to label infarct volume. The levels of MDA and LPO were measured with a biochemical assay. All other items were determined by Western blotting.
Results: Minocycline decreased cerebral infarct volume, but had no effects on neurological scores. Minocycline improved the biological activity of GPx-1/2, GSS and GR, while limited the GGT1 activity in the hippocampus of cerebral ischemia-reperfusion rats. Minocycline also elevated the biological activity of SOD and counteracted lipid peroxidation. Minocycline enhanced the activity of both LKB1 and the levels of the three AMPK subunits in the hippocampus of cerebral ischemia-reperfusion rats.
Conclusion: Minocycline effectively inhibits oxidative stress via modulating antioxidative enzymes and activating the LKB1/AMPK signaling pathway in the process of acute cerebral infarct.
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Cite this article as:
An Antioxidant Role by Minocycline Via Enhancing the Activation of LKB1/AMPK Signaling in the Process of Cerebral Ischemia Injury, Current Molecular Medicine 2018; 18 (3) . https://dx.doi.org/10.2174/1566524018666180907161504
DOI https://dx.doi.org/10.2174/1566524018666180907161504 |
Print ISSN 1566-5240 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5666 |
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