MicroRNA-93 regulates the neurological function, cerebral edema and neuronal apoptosis of rats with intracerebral hemorrhage through TLR4/NF-κB signaling pathway

Abstract

In recent years, many studies have unraveled the impact of microRNAs (miRNAs) in intracerebral hemorrhage (ICH). This study aims to explore the role of miR-93 in modulating neurological function, cerebral edema and neuronal apoptosis of rats with ICH by regulating TLR4/NF-κB signaling pathway. ICH models were constructed using Ⅶ collagenase method. The successfully modeled rats were injected with miR-93 antagomir, TLR4/NF-κB signaling pathway activator or inhibitor together with their controls. The expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and vascular endothelial growth factor (VEGF) was measured using enzyme-linked immunosorbent assay (ELISA). The expression of human aquaporin 4 (AQP-4), Caspase-3, Bax, Bcl-2 and TLR4/NF-κB signaling pathway-related proteins was also measured. MiR-93, TLR4 and NF-κB were all highly expressed in ICH, reduced miR-93 and inhibited TLR4/NF-κB signaling pathway could improve neurological function and suppress inflammation in ICH rats. Moreover, down-regulated miR-93 and suppressed TLR4/NF-κB signaling pathway were able to attenuate cerebral edema and abate pathological lesion. We have also found in this research that miR-93 knockdown as well as inhibited TLR4/NF-κB signaling pathway could relieve neuronal apoptosis in ICH rats. This study suggests that reduced miR-93 alleviates the neurological function and cerebral edema as well as repressed neuronal apoptosis of ICH rats via the inhibited activation of TLR4/NF-κB signaling pathway.