Downregulation of microRNA-200c-3p reduces damage of hippocampal neurons in epileptic rats by upregulating expression of RECK and inactivating the AKT signaling pathway
Downregulation of microRNA-200c-3p reduces damage of hippocampal neurons in epileptic rats by upregulating expression of RECK and inactivating the AKT signaling pathway
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DOI：
10.1016/j.cbi.2019.04.027
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发表时间：
2019-07-01
影响因子：
5.1
通讯作者：
An, Wen
中科院分区：
文献类型：
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作者：
Du, Yumin;Chi, Xiaowen;An, Wen
目的：本研究旨在探讨mircoRNA-200c-3p （miR-200c-3p）通过靶向RECK调控AKT信号通路在癫痫大鼠海马神经元损伤中的作用。方法：采用氯化锂-匹罗卡品腹腔注射致痫大鼠模型。成功建模的大鼠注射miR-200c-3p抑制剂、抑制剂NC、sirna阴性对照（NC）和RECK-siRNA。观察海马组织星形胶质细胞活化、氧化应激指标水平、炎症因子及AKT信号通路相关蛋白含量。结果：癫痫大鼠海马组织中miR-200c-3p高表达，RECK低表达。下调miR-200c-3p或上调RECK可降低癫痫大鼠海马组织中神经元凋亡、GFAP表达、MDA含量，升高GSH-Px、SOD活性，降低tnf - α、IL-1 β、IL-6表达，降低p-PI3K/t-PI3K、p-Akt/t-Akt表达。结论：我们的研究提供了证据，表明下调miR-200c-3p通过上调RECK和抑制AKT信号通路来减轻癫痫大鼠海马神经元的损伤。
Objective: The aim of this study is to investigate the role of mircoRNA-200c-3p (miR-200c-3p) on hippocampal neuron injury in epileptic rats through the regulation of the AKT signaling pathway by targeting RECK.Methods: The epilepsy rat model was induced by intraperitoneal injection of lithium chloride-pilocarpine. Successful modeled rats were injected with miR-200c-3p inhibitors, inhibitors NC, siRNA-negative control (NC) and RECK-siRNA. The astrocyte activation, levels of oxidative stress indexes, contents of inflammatory factors and the AKT signaling pathway-related proteins in hippocampus tissues were evaluated.Results: High expression of miR-200c-3p and low expression of RECK were found in the hippocampus tissues of epileptic rats. Downregulation of miR-200c-3p or upregulation of RECK decreased apoptosis of hippocampal neurons, expression of GFAP, content of MDA and increased the activities of GSH-Px and SOD, decreased expression of TNF-alpha, IL-1 beta and IL-6 as well as expression of p-PI3K/t-PI3K and p-Akt/t-Akt in hippocampus tissues of epileptic rats.Conclusion: Our study provides evidence that downregulation of miR-200c-3p reduces damage of hippocampal neurons in epileptic rats by upregulating RECK and inactivating the AKT signaling pathway.