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基因沉默的肌球蛋白II促进大鼠脊髓挫伤性损伤后的轴突再生。

Gene silencing NMII promotes axonal regeneration against contusive spinal cord injury in rats.

作者信息

Ning Guangzhi, Liu Yang, Xu Hong, Li Yulin, Wu Hong, Wang Xiaobo, Feng Shiqing

机构信息

Department of Orthopedics, Tianjin Medical University General Hospital Tianjing, China.

Tianjin Neurological Institute, Key Laboratory of Post-Neuroinjury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City Tianjin, China.

出版信息

Int J Clin Exp Pathol. 2017 Nov 1;10(11):11345-11352. eCollection 2017.

Abstract

There are drastic changes that occur in the impaired regions after spinal cord injury (SCI), however, improvement of the detrimental pathological process after injury is limited in the mammalian adult, which is due a large part to the failure of local axons to grow. Non-muscle myosin II (NMII) has been proved having essential role in the regulation of cytoskeletal structure and genetic silencing NMII markedly accelerates axon growth in vitro. Our purpose is to explore the association between phosphorylated NMII expression and axonal regeneration after SCI in rats and determine whether gene silencing NMII can improve the locomotor function in rats with SCI. The results showed that phosphorylated NMII level was up regulated after SCI and may even play important role in inhibiting neuronal survival and axonal regeneration. After silencing NMII, the viability of neurons, proliferation of axons, synaptic connection and locomotor functional recovery were promoted significantly after SCI. Our study provides an effective way by direct regulation of neuron viability, the proliferation of axons and synaptic connection for treating SCI, which may be a novel method for repairing SCI. However, the specific signaling pathway mechanisms about the recovery require further study.

摘要

脊髓损伤(SCI)后受损区域会发生剧烈变化,然而,在成年哺乳动物中,损伤后有害病理过程的改善是有限的,这在很大程度上是由于局部轴突无法生长。非肌肉肌球蛋白II(NMII)已被证明在细胞骨架结构调节和基因沉默中起重要作用,NMII在体外显著加速轴突生长。我们的目的是探讨大鼠脊髓损伤后磷酸化NMII表达与轴突再生之间的关联,并确定沉默NMII基因是否能改善脊髓损伤大鼠的运动功能。结果表明,脊髓损伤后磷酸化NMII水平上调,甚至可能在抑制神经元存活和轴突再生中起重要作用。沉默NMII后,脊髓损伤后神经元活力、轴突增殖、突触连接和运动功能恢复均得到显著促进。我们的研究通过直接调节神经元活力、轴突增殖和突触连接提供了一种治疗脊髓损伤的有效方法,这可能是一种修复脊髓损伤的新方法。然而,关于恢复的具体信号通路机制需要进一步研究。

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