Melatonin ameliorates cerebral ischemia/reperfusion injury through SIRT3 activation

  • Life Sci. 2019 Dec 15;239:117036. doi: 10.1016/j.lfs.2019.117036.
Lili Liu  1 ,  Hongping Chen  1 ,  Jing Jin  1 ,  Zhanbin Tang  1 ,  Pengqi Yin  1 ,  Di Zhong  2 ,  Guozhong Li  3
Affiliations
  • 1. Department of Neurology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin, 150001, Heilongjiang Province, PR China.
  • 2. Department of Neurology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin, 150001, Heilongjiang Province, PR China. Electronic address: [email protected].
  • 3. Department of Neurology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin, 150001, Heilongjiang Province, PR China. Electronic address: [email protected].
PMID: 31697951 DOI: 10.1016/j.lfs.2019.117036
Abstract

Aims: Previous literature has shown that melatonin plays a critical role in protecting against cerebral ischemia/reperfusion (I/R) injury. Sirtuin3(SIRT3), as one member of the Sirtuin family, protects against oxidative stress-related diseases. However, the association between melatonin and SIRT3 in cerebral I/R injury is not well understood. Our experiment was planned to investigate whether melatonin protects against cerebral I/R injury through SIRT3 activation.

Main methods: We selected transient middle cerebral artery occlusion (tMCAO) mice as the model of cerebral I/R injury. Male C57/BL6 mice were pre-treated with or without a selective SIRT3 Inhibitor and then subjected to tMCAO surgery. Melatonin (20 mg/kg) was given to mice by intraperitoneal injection after ischemia and before reperfusion. Then, we observed the changes in the SIRT3 and downstream relative proteins, infarction volume, neurological score, Nissl, H&E and TUNEL staining, and the expression of Apoptosis proteins after tMCAO.

Key findings: Melatonin upregulated the expression of SIRT3 after tMCAO, and alleviated the neurological dysfunction and cell Apoptosis through SIRT3 activation.

Significance: Our research proved that melatonin promoted SIRT3 expression after tMCAO and alleviated cerebral I/R injury by activating the SIRT3 signaling pathway. This study provides novel therapeutic targets and mechanisms for the treatment of ischemic stroke in the clinic, especially during cerebrovascular reperfusion.

Keywords
Apoptosis; Ischemia-reperfusion injury; Melatonin; SIRT3.
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