Jiang Guohui, Zhou Ruijiao, He Xuzhi, Shi Zhiqing, Huang Min, Yu Juming, Wang Xiaoming
a 1 Department of Neurology, Institute of Neurology, Affiliated Hospital of North Sichuan Medical College , Wen Hua Road, Nanchong 637000 , China.
b 2 Department of Neurosurgery, Daping Hospital and Institute of Surgery Research, Third Military Medical University , Chongqing 400042 , China.
Int J Neurosci. 2016;126(4):326-34. doi: 10.3109/00207454.2014.994209. Epub 2015 Sep 30.
During the last decade, experimental evidence has demonstrated an important role of hypoxia, which leads to neuronal cell death and angiogenesis, in the mechanisms of seizure precipitation and recurrence. MicroRNA-199 targets hypoxia-inducible factor-1alpha (HIF-1α), which has recently been implicated in the pathophysiology of the hypoxic state and brain injury. However, little is known about the roles of MicroRNA-199 and HIF-1α in the human epileptogenic process.
In this study, we investigated the expression of miR-199a-5p, miR-199b-5p and HIF-1α using real-time PCR, immunohistochemistry and western blots in the temporal neocortex of twenty four patients with intractable epilepsy and twelve control subjects.
Compared with the control group, the expression of miR-199a-5p and miR-199b-5p was significantly lower in epileptic brain tissues (p < 0.05). The levels of HIF-1α mRNA and protein were highly up-regulated in epileptic brain tissues compared with those of control subjects (p < 0.05).
These data suggest that the abnormal expression of miR-199 and HIF-1α in epileptic brain tissue may be involved in the pathophysiology of human epilepsy and that the expression of HIF-1α may be regulated by miR-199. These findings may provide new insights into the treatment of epilepsy.
在过去十年中，实验证据表明缺氧在癫痫发作诱发和复发机制中起重要作用，缺氧会导致神经元细胞死亡和血管生成。微小RNA-199靶向缺氧诱导因子-1α（HIF-1α），最近研究表明HIF-1α与缺氧状态和脑损伤的病理生理学有关。然而，关于微小RNA-199和HIF-1α在人类癫痫发生过程中的作用知之甚少。
在本研究中，我们采用实时聚合酶链反应、免疫组织化学和蛋白质印迹法，检测了24例难治性癫痫患者和12例对照者颞叶新皮质中miR-199a-5p、miR-199b-5p和HIF-1α的表达。
与对照组相比，癫痫脑组织中miR-199a-5p和miR-199b-5p的表达显著降低（p < 0.05）。与对照者相比，癫痫脑组织中HIF-1α mRNA和蛋白质水平显著上调（p < 0.05）。
这些数据表明，癫痫脑组织中miR-199和HIF-1α的异常表达可能参与了人类癫痫的病理生理过程，且HIF-1α的表达可能受miR-199调控。这些发现可能为癫痫治疗提供新的见解。
