Overexpression of miR-381-3p promotes the recovery of spinal cord injury

OBJECTIVE: To study the effects of miR-381-3p on spinal cord injury and its underlying mechanism.

MATERIALS AND METHODS: After the spinal cord injury rat model of was established, Sprague Dawley (SD) rats were randomly divided into the control group and the acute spinal cord injury (ASCI) group. Microglial BV2 cells were used as experimental cells, and the cells were divided into the control group and the lipopolysaccharide (LPS) group. The mRNA and protein expression level of miR-381-3p, IKKβ, inflammatory factors, and p-p65 were detected by quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR) and Western blot, respectively. Dual-luciferase reporter gene assay and Western blot were used to detect the regulatory effect of IKKβ on miR-381-3p. Changes in grip ability and rotary performance of rats in the ASCI group were evaluated after miR-381-3p overexpression in vivo.

RESULTS: The expression of miR-381-3p was downregulated in rats of the ASCI group, while the expression of IKKβ and p-p65 were upregulated. In vitro experiments demonstrated that LPS could inhibit the expression of miR-381-3p and promote the upregulation of IKKβ and p-p65. Overexpression of miR-381-3p could inhibit the mRNA and protein expression of IKKβ. The upregulated expression of IKKβ, p-p65, tumor necrosis factor-alpha (TNF-α), and interleukins-1β (IL-1β) induced by LPS in BV2 cells were reversed by miR-381-3p mimic transfection. Besides, upregulated TNF-α and IL-1β induced by miR-381-3p inhibitor in BV2 cells were reversed by IKKβ inhibitor (BMS-345541). Results of animal experiments indicated that miR-381-3p was overexpressed in rats of the ASCI group. The protein levels of IKKβ and p-p65, and the mRNA expression levels of inflammatory cytokines TNF-α and IL-1β were remarkably decreased in the ASCI group than those of the control group. The grip ability, coordination, and anti-fatigue performance of rats in the ASCI group recovered quicker than those of the control group.

CONCLUSIONS: MiR-381-3p was downregulated in ASCI rats. The overexpression of miR-381-3p could recover the motor ability of rats in the ASCI group earlier and might inhibit injury aggravation by inhibiting inflammatory responses via the IKKβ-NF-κB pathway.

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