Protective role of microRNA-27a upregulation and HSP90 silencing against cerebral ischemia-reperfusion injury in rats by activating PI3K/AKT/mTOR signaling pathway.

Objective: MicroRNAs (miRNAs) have been reported in cerebral ischemia-reperfusion injury, yet the function of miR-27a in it has seldom been mentioned. This study aims to assess the mechanisms of miR-27a in rats with cerebral ischemia-reperfusion injury.

Methods: The cerebral ischemia-reperfusion models of rat pups were established by bilateral carotid artery occlusion. Rats were treated with miR-27a agomir, silenced HSP90 expression plasmids or PI3K/AKT/mTOR pathway agonist. Oxidative stress indices, inflammatory factors, brain tissue water content, cerebral infarct volume, neurological function score and neuronal apoptosis in rats with cerebral ischemia-reperfusion injury were measured. MiR-27a and HSP90 expression and PI3K/AKT/mTOR phosphorylation levels in the brain tissues of rats were also detected.

Results: MiR-27a expression and PI3K/AKT/mTOR phosphorylation levels were downregulated while HSP90 expression was upregulated in cerebral ischemia-reperfusion injury rats. Elevated miR-27a or reduced HSP90 diminished water content, neuronal apoptosis and infarct volume, suppressed oxidative stress and inflammatory response, as well as improved neurological deficits and pathological damages. Moreover, elevated miR-27a or silenced HSP90 upregulated PI3K/AKT/mTOR phosphorylation levels in cerebral ischemia-reperfusion injury rats. HSP90 silencing or PI3K/AKT/mTOR pathway agonist reversed the unfavorable effects of low miR-27a expression on cerebral ischemia-reperfusion injury rats.

Conclusions: To conclude, our study demonstrates that elevated miR-27a or decreased HSP90 attenuates oxidative stress and inflammatory response, and improves neurological function in cerebral ischemia-reperfusion injury rats by activating PI3K/AKT/mTOR signaling pathway.