Department of Obstetrics and Gynecology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, P.R. China.
Department of Neurology, Guangzhou Hospital of TCM, Guangzhou Medical University, Guangzhou, Guangdong 510130, P.R. China.
Int J Mol Med. 2021 Jun;47(6). doi: 10.3892/ijmm.2021.4931. Epub 2021 Apr 13.
Researchers have confirmed the microRNA (miRNA/miR)‑epilepsy association in rodent models of human epilepsy via a comprehensive database. However, the mechanisms of miR‑142 in epilepsy have not been extensively studied. In the present study, a rat model of epilepsy was first established by an injection of lithium chloride‑pilocarpine and the successful establishment of the model was verified via electroencephalogram monitoring. The levels of miR‑142, phosphatase and tensin homolog deleted on chromosome 10 (PTEN)‑induced putative kinase 1 (PINK1), marker proteins of mitochondrial autophagy, and apoptosis‑related proteins were measured. Additionally, the pathological changes in the hippocampus, the ultrastructure of the mitochondria, and degeneration and the apoptosis of neurons were observed using different staining methods. The malondialdehyde (MDA) content and superoxide dismutase (SOD) activity in the hippocampus, mitochondrial membrane potential (MTP) and reactive oxygen species (ROS) generation were detected. Furthermore, the targeting association between miR‑142 and PINK1 was predicted and verified. Consequently, apoptosis increased, and mitochondrial autophagy decreased, in the hippocampus of epileptic rats. Following miR‑142 inhibition, the epileptic rats exhibited an increased Bax expression, a decreased Bcl‑2 expression, upregulated marker protein levels of mitochondrial autophagy, a reduced MDA content, an enhanced SOD activity, an increased MTP and decreased ROS generation. PINK1 is a target gene of miR‑142, and its overexpression protected against hippocampal damage. Taken together, the results of the present study demonstrated that miR‑142 inhibition promotes mitochondrial autophagy and reduces hippocampal damage in epileptic rats by targeting PINK1. These findings may provide useful information for the treatment of epilepsy.
研究人员通过综合数据库证实了微小 RNA (miRNA/miR) 与人类癫痫啮齿动物模型之间的关联。然而,miR-142 在癫痫中的机制尚未得到广泛研究。本研究首先通过氯化锂-匹罗卡品注射建立了癫痫大鼠模型,并通过脑电图监测验证了模型的成功建立。测量了 miR-142、磷酸酶和张力蛋白同源物缺失的 10 号染色体 (PTEN) 诱导的假定激酶 1 (PINK1)、线粒体自噬的标志物蛋白和凋亡相关蛋白的水平。此外,还使用不同的染色方法观察了海马体的病理变化、线粒体的超微结构、神经元的变性和凋亡。检测了海马体中的丙二醛 (MDA) 含量和超氧化物歧化酶 (SOD) 活性、线粒体膜电位 (MTP) 和活性氧 (ROS) 的产生。此外,还预测和验证了 miR-142 和 PINK1 之间的靶向关联。结果表明,癫痫大鼠海马体中凋亡增加,线粒体自噬减少。抑制 miR-142 后,癫痫大鼠 Bax 表达增加,Bcl-2 表达减少,线粒体自噬标志物蛋白水平升高,MDA 含量降低,SOD 活性增强,MTP 升高,ROS 生成减少。PINK1 是 miR-142 的靶基因,过表达可保护海马体免受损伤。综上所述,本研究结果表明,抑制 miR-142 通过靶向 PINK1 促进癫痫大鼠的线粒体自噬,减轻海马体损伤。这些发现可能为癫痫的治疗提供有用的信息。