Department of Neurology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang Medical University, 88 Road of JianKang, WeiHui, Xinxiang 453100, PR China; Department of Neurology, Beijing Tiantan Hospital, Capital Medical University; China National Clinical Research Center for Neurological Diseases, 6 TianTanXiLi, Dongcheng District, Beijing 100050, PR China.
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, 1 East Road of JianShe, Erqi District, Zhengzhou 450052, PR China.
Brain Res. 2018 Dec 1;1700:56-65. doi: 10.1016/j.brainres.2018.07.013. Epub 2018 Jul 11.
Accumulative evidence demonstrates that there is an inseparable connection between inflammation and temporal lobe epilepsy (TLE). Some recent studies have found that the multifunctional microRNA-155 (miR-155) is a key regulator in controlling the neuroinflammatory response of TLE rodent animals and patients. The aim of the present study was to investigate the dynamic expression pattern of tumor necrosis factor alpha (TNF-α) as a pro-inflammatory cytokine and miR-155 as a posttranscriptional inflammation-related miRNA in the hippocampus of TLE rat models and patients. We performed real-time quantitative PCR (qRT-PCR) on the rat hippocampus 2 h, 7 days, 21 days and 60 days following kainic acid-induced status epilepticus (SE) and on hippocampi obtained from TLE patients and normal controls. To further characterize the relationship between TNF-α and miR-155, we examined the effect of antagonizing miR-155 on TNF-α secretion using its antagomir. Here, we found that TNF-α secretion and miR-155 expression levels were correlated after SE. The expression of TNF-α reached peak levels in the acute phase (2h post-SE) of seizure and then gradually decreased; however, it rose again in the chronic phase (60 days post-SE). miR-155 expression started to increase 2 h post-SE, reached peak levels in the latent phase (7 days post-SE) of seizure and then gradually decreased. The variation in the trend of miR-155 lagged behind that of TNF-α. In patients with TLE, the expression levels of both TNF-α and miR-155 were also significantly increased. Furthermore, antagonizing miR-155 inhibited the production of TNF-α in the hippocampal tissues of TLE rat models. Our findings demonstrate a critical role for miR-155 in the physiological regulation of the TNF-α pro-inflammatory response and elucidate the role of neuroinflammation in the pathogenesis of TLE. Therefore, regulation of the miR-155/TNF-α axis may be a new therapeutic target for TLE.
越来越多的证据表明，炎症与颞叶癫痫（TLE）之间存在不可分割的联系。一些最近的研究发现，多功能 microRNA-155（miR-155）是控制 TLE 啮齿动物动物和患者神经炎症反应的关键调节剂。本研究旨在研究肿瘤坏死因子 alpha（TNF-α）作为促炎细胞因子和 miR-155 作为转录后炎症相关 miRNA 在 TLE 大鼠模型和患者海马体中的动态表达模式。我们对红藻氨酸诱导的癫痫持续状态（SE）后大鼠海马体 2 h、7 d、21 d 和 60 d 以及 TLE 患者和正常对照组的海马体进行实时定量 PCR（qRT-PCR）。为了进一步描述 TNF-α 和 miR-155 之间的关系，我们使用其拮抗剂检查了拮抗 miR-155 对 TNF-α 分泌的影响。在这里，我们发现 SE 后 TNF-α 分泌和 miR-155 表达水平相关。TNF-α 的表达在发作的急性期（SE 后 2 h）达到峰值，然后逐渐下降；然而，它在慢性期（SE 后 60 天）再次升高。miR-155 的表达在 SE 后 2 h 开始增加，在潜伏期（SE 后 7 天）达到峰值，然后逐渐下降。miR-155 变化的趋势滞后于 TNF-α。在 TLE 患者中，TNF-α 和 miR-155 的表达水平也明显升高。此外，拮抗 miR-155 抑制了 TLE 大鼠模型海马组织中 TNF-α 的产生。我们的研究结果表明，miR-155 在 TNF-α 促炎反应的生理调节中起关键作用，并阐明了神经炎症在 TLE 发病机制中的作用。因此，调节 miR-155/TNF-α 轴可能是 TLE 的新治疗靶点。
