MicroRNA-592 (miR-592) has been reported to play a significant role in mediating neuronal activity, but its possible link with Alzheimer's disease (AD) remains unclear. We aimed to explore the mechanism of miR-592 in oxidative stress (OS) injury of astrocytes (ASTs) from AD rat models induced by D-galactose or Aβ25-35 injection. Bioinformatics website and dual-luciferase reporter gene assay clarified the binding affinity between miR-592 and KIAA0319. KIAA0319 was identified as a target gene of miR-592. The mechanism of miR-592, KIAA0319 and the Keap1/Nrf2/ARE signaling pathway in AD was examined after transducing miR-592 mimic, miR-592 inhibitor and siRNA-KIAA0319 into ASTs to query cell viability, OS injury and reactive oxygen species (ROS). The rat models of AD Exhibited highly expressed miR-592 and poorly expressed KIAA0319. Furthermore, inhibition of miR-592 diminished C-Keap1 expression and enhanced N-Nrf2 and NQO1 expression, thus promoting cell viability and reducing OS injury of ASTs. Taken together, these findings suggested that the downregulation of miR-592 inhibited OS injury of ASTs in rat models of AD by up-regulating KIAA0319 through the activation of the Keap1/Nrf2/ARE signaling pathway.

中文翻译：

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microRNA-592阻滞剂通过KIAA0319介导的Keap1 / Nrf2 / ARE信号通路抑制阿尔茨海默氏病星形胶质细胞的氧化应激损伤。

据报道，MicroRNA-592（miR-592）在介导神经元活动中起重要作用，但其与阿尔茨海默氏病（AD）的可能联系尚不清楚。我们旨在探讨miR-592在D-半乳糖或Aβ25-35注射诱导的AD大鼠模型中星形胶质细胞（AST）氧化应激（OS）损伤中的机制。生物信息学网站和双荧光素酶报告基因检测阐明了miR-592与KIAA0319之间的结合亲和力。KIAA0319被鉴定为miR-592的靶基因。在将miR-592模拟物，miR-592抑制剂和siRNA-KIAA0319转化为AST以查询细胞活力，OS损伤和活性氧种类之后，检查了miR-592，KIAA0319和Keap1 / Nrf2 / ARE信号通路在AD中的机制。 ROS）。AD的大鼠模型表现出高表达的miR-592和低表达的KIAA0319。此外，抑制miR-592可减少C-Keap1表达并增强N-Nrf2和NQO1表达，从而促进细胞活力并减少AST的OS损伤。综上，这些发现表明，miR-592的下调通过激活Keap1 / Nrf2 / ARE信号通路上调了KIAA0319，从而抑制了AD大鼠模型中AST的OS损伤。