Highlights
- •We find the neuroprotective effect of nicorandil in the mouse model of deep hypothermic low flow.
- •We describe the anti-apoptosis effect of nicorandil with the findings of HE staining, TUNEL staining and Western blot.
- •We elucidate that the possible mechanism of nicorandil under DHLF is mediated by the PI3K/Akt1 signaling pathway.
- •We refer to nicorandil could be potential therapeutic agents for the treatment of brain I/R injury after DHLF.
Abstract
Objective
Nicorandil exerts a protective effect on ischemia–reperfusion (I/R) injury in the
brain and kidney through anti-apoptotic mechanisms. However, the mechanism by which
nicorandil protects against I/R injury induced by deep hypothermic low flow (DHLF)
remains unclear.
Methods
We used a cerebral I/R model induced by DHLF to determine the neuroprotective effects
and possible mechanisms of nicorandil.
Results
Hematoxylin–eosin (HE) staining and in situ terminal deoxynucleotidyl transferase
UTP nick end labeling (TUNEL) assay were used to detect changes in cell morphology
and the number of apoptotic cells in hippocampus, respectively. The apoptotic regulators
including Bcl-2, Bax, Akt, and p-Akt (the active, phosphorylated form of Akt) were
examined by Western blot (WB). Histopathological findings showed that nicorandil significantly
alleviated morphological damage in hippocampal and reduced the number of TUNEL-positive
nuclei induced by DHLF. Nicorandil also increased the expression of Bcl-2 and decreased
the expression of Bax, while increasing p-Akt level. Consistent with these results,
nicorandil-mediated neuroprotection was reduced in the Akt1+/− mutant mice and inhibited by LY294002, a PI3K inhibitor.
Conclusions
These findings showed that nicorandil provides a neuroprotective role in DHLF-induced
I/R injury by inhibiting apoptosis via activation of the PI3K/Akt1 signaling pathway.
Keywords
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Article info
Publication history
Published online: July 08, 2015
Accepted:
July 7,
2015
Received in revised form:
June 16,
2015
Received:
May 5,
2015
Identification
Copyright
© 2015 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
