Melatonin improves hypoxic-ischemic brain damage through the Akt/Nrf2/Gpx4 signaling pathway

被引：95
|
作者：
Gou, Zhixian [1 ]
Su, Xiaojuan [2 ]
Hu, Xing [1 ]
Zhou, Yue [1 ]
Huang, Lin [1 ]
Fan, Yang [1 ]
Li, Jing [3 ]
Lu, Liqun [1 ]
机构：
[1] Chengdu Med Coll, Affiliated Hosp 1, Dept Pediat, Chengdu 610500, Sichuan, Peoples R China
[2] Sichuan Univ, West China Univ Hosp 2, Dept Pediat, Minist Educ,Key Lab Birth Defects & Related Dis W, Chengdu 610041, Peoples R China
[3] Chengdu Med Coll, Affiliated Hosp 1, Clin Lab, Chengdu 610500, Sichuan, Peoples R China
来源：
BRAIN RESEARCH BULLETIN | 2020年 / 163卷
关键词：
Melatonin; Hypoxic-ischemic brain damage; Neuron; Ferroptosis; Akt/Nrf2/Gpx4; OXIDATIVE STRESS; INJURY; ENCEPHALOPATHY; METABOLISM; MECHANISMS; ABLATION;
D O I：
10.1016/j.brainresbull.2020.07.011
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
Melatonin (Mel) has neuroprotective effects; however, its roles in hypoxic-ischemic brain damage (HIBD) and the underlying mechanisms remain unknown. We aimed to explore its roles and mechanisms in a HIBD rat model. We found that exogenous Mel treatment ameliorated HIBD-induced pathological changes, inhibited neuronal ferroptosis, and promoted hippocampal neuronal survival. Moreover, Mel improved the learning and memory abilities of the HIBD rats. Further, we found that glutathione peroxidase 4 (Gpx4) inhibition with RSL3, Akt inhibition with LY29400, and nuclear factor erythroid-2-related factor 2 (Nrf2) inhibition with ML385 abolished the Mel protective effects in HIBD. Our findings indicate that exogenous Mel treatment has a protective effect on HIBD via the Akt/Nrf2/Gpx4 pathway.
引用
收藏
页码：40 / 48
页数：9
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