Antagonist targeting microRNA-146a protects against lithium-pilocarpine-induced status epilepticus in rats by nuclear factor-κB pathway.
Antagonist targeting microRNA-146a protects against lithium-pilocarpine-induced status epilepticus in rats by nuclear factor-κB pathway.
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DOI：
10.3892/mmr.2018.8465
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发表时间：
2018-04
影响因子：
3.4
通讯作者：
Huilong Zhang;Y. Qu;Aihua Wang
中科院分区：
文献类型：
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作者：
Huilong Zhang;Y. Qu;Aihua Wang
既往研究表明核因子-κB（NF-κB）在癫痫的发病机制中具有重要作用。本研究的目的是评估癫痫大鼠脑组织中微小RNA (miRNA)-146a、磷酸化(p)-P65/P65、B细胞淋巴瘤-2(Bcl-2)/Bcl-2相关X蛋白(Bax)和促炎细胞因子，如白细胞介素(IL)-6、IL-1β和肿瘤坏死因子(TNF-α)的表达。 Sprague-Dawley大鼠采用锂-毛果芸香碱法建立癫痫模型。分别通过逆转录半定量聚合酶链反应、酶联免疫吸附测定和蛋白质印迹评估miR-146a、促炎细胞因子、P-糖蛋白（P-gp）、Bcl-2/Bax和p-P65/P65的表达。苏木精和伊红染色用于确定癫痫的病理学。目前的研究结果显示，与对照组相比，模型组中miR-146a的表达量更高，并且在治疗后7天时miR-146a的表达量达到最大值。与模型组相比，miR-146a拮抗剂组IL-1β、IL-6和TNF-α的表达水平显着降低。此外，添加miR-146a拮抗剂后，P-gp和p-P65/P65的表达水平显着降低，而Bcl-2/Bax的表达水平在相同条件下显着增加。因此，NF-κB通路和miR-146a可能是癫痫治疗的潜在治疗靶点。
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.