MiR-379-5p improved locomotor function recovery after spinal cord injury in rats by reducing endothelin 1 and inhibiting astrocytes expression
MiR-379-5p improved locomotor function recovery after spinal cord injury in rats by reducing endothelin 1 and inhibiting astrocytes expression
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DOI：
10.26355/eurrev_201911_19536
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发表时间：
2019-01-01
影响因子：
3.3
通讯作者：
Zhang, W-H.
中科院分区：
文献类型：
--
作者：
Li, Z-Y.;Long, Q-F.;Zhang, W-H.
目的：本研究旨在探讨microRNA-214- 5 p（miR-214- 5 p）在脊髓损伤（spinal cord injury，SCI）中的作用及其病理生理学意义。1个月后采用BBB运动功能评定量表检测miR-379- 5 p组和SCI组大鼠运动功能恢复水平。生化指标分别采用Western blotting和真实的time-PCR检测。结果：与脊髓损伤组相比，miR-379 - 5 p组大鼠在体运动功能明显改善。MiR-379- 5 p可减弱星形胶质细胞的活化，并显著抑制神经生长抑制因子的表达。此外，下调内皮素-1（ET-1）可改善脊髓缺血，从而减少细胞凋亡和氧化应激。结论：miR-379 - 5 p通过抑制ET-1和星形胶质细胞的表达，延缓SCI后神经丝再生阻滞效应。此外，它可能减轻神经结构的破坏，抗氧化应激，抑制细胞凋亡，最终促进功能恢复。
OBJECTIVE: The aim of this study was to investigate the effect of microRNA-214-5p (miR-214-5p) on spinal cord injury (SCI) and to explore the mechanism of action in pathophysiological relevance.MATERIALS AND METHODS: The model of SCI was successfully established in rats aged 6-8 weeks. The levels of the locomotor function recovery in rats of the miR-379-5p group and SCI group were detected one month later by Basso-Beattie-Bresnahan (BBB) locomotor rating scale. Biochemical indexes were measured by Western blotting and real time-PCR, respectively. In addition, rat astrocytes were cultured to verify the effect of miR-379-5p on activated astrocytes in vitro.RESULTS: Compared with the SCI group, the rats in the miR-379-5p group showed prominent improvement in the locomotor function in vivo. MiR-379-5p attenuated the activation of astrocytes and significantly suppressed the expressions of the nerve growth inhibitors. Furthermore, the down-regulation of endothelin-1 (ET-1) ameliorated the spinal cord ischemia, thereby reducing apoptosis and oxidative stress. Compared with the pentylenetetrazol (PTZ) group, ET-1 and chondroitin sulfate poly-glycoprotein (CSPG) in miR-379-5p group decreased significantly in the astrocytes transfected with miR-214-5p in vitro.CONCLUSIONS: MiR-379-5p retarded the neurofilament regeneration block effect by inhibiting endothelin 1 and the expression of the astrocytes after SCI. Furthermore, it might relieve nerve structure destruction, resist oxidative stress, and inhibit apoptosis, eventually promoting functional recovery.