miRNA-146a/CFH介导的炎症通路在颞叶癫痫炎症持续存在中的作用

Recently, accumulating evidence support that inflammation is widely present in the brain tissue of patients with temporal lobe epilepsy (TLE), which plays a key role in the pathophysiology of TLE. However, it is not very clear how the perpetuate inflammation develops. Some recent studies suggested the possible involvement of miRNA-146a in the modulation of inflammatory signaling occurring in TLE. Human miRNA-146a was highly complementary to human complement factor H (CFH) mRNA 3'UTR. Upregulation of miRNA-146a accompanied with down-regulation of CFH. Meanwhile our previous research demonstrated upregulation of miRNA-146a and proinflammatory cytokines IL-1β, and down-regulation of CFH expression in resected temporal lobe tissue of TLE patients. Therefore, we hypothesize that high expression of miRNA-146a leads to the increase of proinflammatory cytokines by down-regulation of CFH expression, and increased proinflammatory cytokines upregulate the expression of miRNA-146a in futher, which initiate a cascade of inflammation. This study will explore how miRNA-146a/CFH mediated inflammation signaling pathway plays an role on the perpetuate inflammation of TLE in vivo，using TLE rat model and the CFH knockout rat model. Unveiling the molecular mechanism of the perpetuate inflammation of TLE will provide the theoretical foundation for the treatment of TLE.

近年来，越来越多研究表明炎症广泛存在于颞叶癫痫病人脑组织中，且在其病理生理中扮演着关键的角色，然而，炎症持续存在的机制尚不十分明确。最近的研究提示miRNA-146a可能参与了颞叶癫痫炎症反应的调节。miRNA-146a与补体因子H(CFH)3'端非编码区高度互补，负调控CFH表达水平，结合我们前期研究发现- - -颞叶癫痫病人手术切除的颞叶组织标本中miRNA-146a和前炎症因子IL-1β表达上调、CFH表达下降。因此我们提出假说：颞叶癫痫脑组织高表达的miRNA-146a，有可能通过下调CFH的表达导致IL-1β增多，而增多的IL-1β进一步上调miRNA-146a，从而启动了脑内的炎症级联反应。为证实该假说，本研究采用颞叶癫痫模型鼠和CFH基因敲除的颞叶癫痫模型鼠，利用体内实验探索miRNA-146a/CFH介导的炎症通路在颞叶癫痫炎症持续存在中的作用，从而为治疗颞叶癫痫提供理论依据。

近年来，越来越多研究表明炎症广泛存在于颞叶癫痫病人脑组织中，且在其病理生理中扮演着关键的角色，然而，炎症持续存在的机制尚不十分明确。最近的研究提示miRNA-146a可能参与了颞叶癫痫炎症反应的调节。为了解miRNA-146a调控颞叶癫痫炎症反应的机制，我们在细胞水平和动物水平检测了miRNA-146a、补体因子H（CFH）和IL-1β三者关联。结果表明：在慢性期颞叶癫痫模鼠型海马组织中，增多的miRNA-146a能够上调IL-1β表达水平；减少的miRNA-146a能够下调IL-1β表达水平。增多的miRNA-146a能够下调CFH表达水平和增加异常脑电波。增多的IL-1β可以反馈性下调CFH表达水平、增加miRNA-146a和增加异常脑电波。当敲降CFH后，增多的miRNA-146a并不能够上调IL-1β表达水平。证实了miRNA-146a/CFH/IL-1β炎症通路在颞叶癫痫炎症持续存在中的作用，从而为治疗颞叶癫痫提供理论依据。