MicroR-146 protects against rat ischemia-reperfusion injury by targeting NF-κB-mediated PI3K/AKT/mTOR signaling pathway

Abstract

MicroR-146 (miR-146) plays crucial roles in attenuating nerve injury during cerebral ischemia-reperfusion (I/R) injury. The purpose of this study was to investigate the neuroprotective effect of miR-146 against cerebral I/R injury. Rat model of cerebral I/R injury was established using 4-vessel occlusion and reperfusion. In this study, miR-146 expression was significantly decreased in neurons in cerebral I/R injury rat compared to sham group. In addition, miR-146+/+ significantly decreased inflammatory cytokines, oxidative stress, neuron cell apoptosis and the infarct size in cerebral I/R injury rats (p<0.05). Transfection of miR-146 reduced apoptosis, autophagy and autophagy-related proteins LC-3, Beclin-1 and increased p62 in the neuron cells compared to control group. Furthermore, overexpression of miR-146 was indicated to directly targeting NF-κB and activating PI3K/AKT/ mTOR expression in neuron cells. In conclusion, these findings suggested that miR-146 could protect against rat ischemia-reperfusion injury by targeting NF-κB-mediated PI3K/AKT/mTOR signaling pathway, which offered a potential molecular for the treatment of cerebral I/R injury.