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

被引：110

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

页码：40 / 48

页数：9

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