Downregulation of microRNA-181a-5p Protects Against Intracerebral Hemorrhage by Regulating the Sirtuin 1/Nuclear Factor-κB Signaling Pathway

Abstract

Intracerebral hemorrhage (ICH) is a common cerebrovascular disease. MicroRNA-181a-5p (miR-181a-5p) has been investigated in various diseases. However, till now, the role of miR-181a-5p in ICH remains unclear. The present study was conduct to analyze the function of miR-181a-5p in ICH. First, an ICH rat model was conducted to assess the level of miR-181a-5p in ICH, and the data showed that miR-181a-5p was significantly up-regulated in ICH rat. Then, TargetScan and the dual luciferase reporter gene assay were applied to confirm the association between miR-181a-5p and sirtuin (SIRT)1, and the findings indicated that miR-181a-5p directly targeted SIRT1. The results also indicated that SIRT1 was downregulated in the ICH rat model. Subsequently, the effect of miR-181a-5p deficiency on ICH rats was investigated. It was observed that the miR-181a-5p inhibitor significantly reduced the neurobehavioral scores, brain edema and nerve cell apoptosis in ICH rats. ELISA results suggested that miR-181a-5p inhibitor significantly inhibited the expression of tumor necrosis factor-α and interleukin-1β in the serum and cerebrospinal fluid of ICH rats. In addition, the results demonstrated that the miR-181a-5p inhibitor significantly reduced serum malondialdehyde content and increased superoxide dismutase activity. Western blot assay revealed that the miR-181a-5p inhibitor suppressed the expression of p-p65 and the p-p65/p65 ratio in the brain tissue of ICH rats. Of note, all these results were reversed by SIRT1-siRNA. In conclusion, this study indicated that the miR-181a-5p inhibitor protected against ICH by targeting SIRT1.