Wang Xiaole, Yin Fei, Li Linhong, Kong Huimin, You Baiyang, Zhang Weixi, Chen Shuyuan, Peng Jing
Department of Pediatrics, Xiangya Hospital of Central South University, China.
Department of Pediatrics, Xiangya Hospital of Central South University, China; Hunan Intellectual and Developmental Disabilities Research Center, Pediatrics, China.
Epilepsy Res. 2018 Jan;139:14-19. doi: 10.1016/j.eplepsyres.2017.10.006. Epub 2017 Nov 4.
Status epilepticus (SE) is a common, life-threatening neurological emergency that confers a high degree of morbidity and mortality. Increasing evidence indicates that neuroinflammation plays a critical role in the pathogenesis of SE. MicroRNA-146a (miR-146a) has been reported to be an important posttranscriptional inflammation-associated microRNA. The aim of this study was to investigate the effect of miR-146a in SE and the mechanism by which it operates.
To study the effect of miR-146a in SE, we chose intracerebroventricular injection for rat at 21-28days old, and made a lithium-pilocarpine-induced SE rat model. We assessed latency time and Lado grade by behavior observation. We performed qPCR, ELISA and western blot tests on rat hippocampus to measure the expression levels of miR-146a, IL-1β, TNF-α, TLR4 and NF-κB.
In the miR-146a antagomir injection group, the latency to generalized convulsions was shorter, the duration and degree of seizures were more severe, the expression level of miR-146a was clearly decreased, and IL-1β, TNF-α, TLR4 and NF-κB were all significantly up-regulated. The opposite was true for rats treated with miR-146a agomir.
Our findings elucidate the role of inflammation in the pathogenesis of SE in immature rats, and show that regulating the expression level of miR-146a may provide a novel insights into the pathogenesis of SE.
癫痫持续状态（SE）是一种常见的、危及生命的神经系统急症，具有很高的发病率和死亡率。越来越多的证据表明，神经炎症在SE的发病机制中起关键作用。据报道，微小RNA-146a（miR-146a）是一种重要的转录后炎症相关微小RNA。本研究的目的是探讨miR-146a在SE中的作用及其作用机制。
为研究miR-146a在SE中的作用，我们选择对21-28日龄的大鼠进行脑室内注射，并制作锂-匹罗卡品诱导的SE大鼠模型。通过行为观察评估潜伏期和拉多评分。对大鼠海马进行qPCR、ELISA和蛋白质免疫印迹试验，以检测miR-146a、白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、Toll样受体4（TLR4）和核因子-κB（NF-κB）的表达水平。
在miR-146a反义寡核苷酸注射组中，全身惊厥的潜伏期缩短，癫痫发作的持续时间和程度更严重，miR-146a的表达水平明显降低，IL-1β、TNF-α、TLR4和NF-κB均显著上调。用miR-146a激动剂处理的大鼠则相反。
我们的研究结果阐明了炎症在幼鼠SE发病机制中的作用，并表明调节miR-146a的表达水平可能为SE的发病机制提供新的见解。
