Department of Orthopedics, Qinghai Red Cross Hospital, Xining, China.
Eur Rev Med Pharmacol Sci. 2019 Nov;23(22):9738-9745. doi: 10.26355/eurrev_201911_19536.
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.
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.
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.
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.
本研究旨在探讨微小 RNA-214-5p（miR-214-5p）对脊髓损伤（SCI）的影响，并探讨其在病理生理学相关性中的作用机制。
成功建立了 6-8 周龄大鼠 SCI 模型。一个月后，通过 Basso-Beattie-Bresnahan（BBB）运动评分量表检测 miR-379-5p 组和 SCI 组大鼠运动功能恢复水平。分别采用 Western blot 和实时 PCR 测定生化指标。此外，培养大鼠星形胶质细胞以验证 miR-379-5p 对体外激活星形胶质细胞的作用。
与 SCI 组相比，miR-379-5p 组大鼠体内运动功能明显改善。miR-379-5p 可减弱星形胶质细胞的激活，显著抑制神经生长抑制剂的表达。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。与戊四氮（PTZ）组相比，miR-379-5p 组 ET-1 和软骨素硫酸盐多聚糖蛋白（CSPG）在体外转染 miR-214-5p 的星形胶质细胞中明显降低。
miR-379-5p 通过抑制内皮素 1 和 SCI 后星形胶质细胞的表达，延缓神经丝再生阻滞效应。此外，它可能减轻神经结构破坏，抵抗氧化应激，抑制细胞凋亡，最终促进功能恢复。
