L-Z Ding1, J Xu, C Yuan, X Teng, Q-M Wu. 1. Department of Orthopedics, Taizhou Central Hospital, Taizhou, China. Gui625625625@163.com.
Abstract
OBJECTIVE: The aim of this study was to investigate the therapeutic effect of microRNA-7a (miR-7a) on spinal cord injured rats and to explore its underlying mechanism in vivo. MATERIALS AND METHODS: The spinal cord injury (SCI) model was first established in adult rats. The epicenter of the lesion was treated with miR-7a mimics via intrathecal injection. The Basso-Beattie-Bresnahan (BBB) locomotor rating scale was used to evaluate the functional recovery of hindlimbs in rats within 4 weeks following SCI. Western blotting and qPCR were utilized to detect the apoptosis and oxidative stress in rats treated with or without miR-7a. In addition, the neuron survival and neuro-filament amount were determined using immunofluorescence. RESULTS: After SCI and miR-7a treatment, the locomotor recovery of treated rats was significantly improved when compared with rats without treatment. The mitochondrial disorder and cell death were significantly reduced in miR-7a treated rats. Meanwhile, the nuclear transcription factor-κB (NF-κB) pathway was significantly reduced as well. Contrarily, the expression of anti-apoptotic protein Bcl-2 and NF-κB inhibitor I-κB was remarkably elevated in miR-7a treated rats. In addition, up-regulation of miR-7a rescued neurons and maintained the neural structure. CONCLUSIONS: The up-regulation of miR-7a alleviated the injury-induced oxidative stress and inhibited apoptosis by down-regulating NF-κB pathway in SCI rats.
OBJECTIVE: The aim of this study was to investigate the therapeutic effect of microRNA-7a (miR-7a) on spinal cord injured rats and to explore its underlying mechanism in vivo. MATERIALS AND METHODS: The spinal cord injury (SCI) model was first established in adult rats. The epicenter of the lesion was treated with miR-7a mimics via intrathecal injection. The Basso-Beattie-Bresnahan (BBB) locomotor rating scale was used to evaluate the functional recovery of hindlimbs in rats within 4 weeks following SCI. Western blotting and qPCR were utilized to detect the apoptosis and oxidative stress in rats treated with or without miR-7a. In addition, the neuron survival and neuro-filament amount were determined using immunofluorescence. RESULTS: After SCI and miR-7a treatment, the locomotor recovery of treated rats was significantly improved when compared with rats without treatment. The mitochondrial disorder and cell death were significantly reduced in miR-7a treated rats. Meanwhile, the nuclear transcription factor-κB (NF-κB) pathway was significantly reduced as well. Contrarily, the expression of anti-apoptotic protein Bcl-2 and NF-κB inhibitor I-κB was remarkably elevated in miR-7a treated rats. In addition, up-regulation of miR-7a rescued neurons and maintained the neural structure. CONCLUSIONS: The up-regulation of miR-7a alleviated the injury-induced oxidative stress and inhibited apoptosis by down-regulating NF-κB pathway in SCIrats.