Antagonist targeting microRNA-146a protects against lithium-pilocarpine-induced status epilepticus in rats by nuclear factor-κB pathway

Abstract

Previous studies have indicated that nuclear factor-κB (NF-κB) has an important role in the pathogenesis of epilepsy. The aim of the present-study was to evaluate the expression of microRNA (miRNA)-146a, phosphorylated (p)-P65/P65, B-cell lymphoma-2(Bcl-2)/Bcl-2-associated X protein (Bax) and pro-inflammatory cytokines, such as interleukin (IL)-6, IL-1β and tumor necrosis factor (TNF-α) in the brain tissue of rats with epilepsy. Sprague-Dawley rats were used to establish the epilepsy model using the lithium-pilocarpine method. The expression of miR-146a, pro-inflammatory cytokines, P-glycoprotein (P-gp), Bcl-2/Bax and p-P65/P65 were assessed by reverse transcription-semi-quantitative polymerase chain reaction, enzyme-linked immunosorbent assay and western blotting, respectively. Hematoxylin and eosin staining was used to determine the pathology of epilepsy. The current findings revealed that the expression of miR-146a was greater in the model group compared with the control group, and that the expression of miR-146a reached a maximum at 7 days post-treatment. The expression levels of IL-1β, IL-6 and TNF-α were significantly reduced in the miR-146a antagonist group when compared with the model group. Additionally, the expression levels of P-gp and p-P65/P65 were significantly reduced following the addition of the miR-146a antagonist, whereas the expression levels of Bcl-2/Bax significantly increased under the same conditions. Therefore, the NF-κB pathway and miR-146a may be potential therapeutic targets in the treatment of epilepsy.