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由聚乙烯亚胺-海藻酸盐纳米颗粒递送的Nischarin小干扰RNA可加速脊髓损伤后运动功能的恢复。

Nischarin-siRNA delivered by polyethylenimine-alginate nanoparticles accelerates motor function recovery after spinal cord injury.

作者信息

Ding Yue-Min, Li Yu-Ying, Wang Chu, Huang Hao, Zheng Chen-Chen, Huang Shao-Han, Xuan Yang, Sun Xiao-Yi, Zhang Xiong

机构信息

Department of Clinical Medicine, School of Medicine, Zhejiang University City College, Hangzhou, Zhejiang Province, China.

Department of Physiology, School of Medicine, Quzhou College of Technology, Quzhou, Zhejiang Province, China.

出版信息

Neural Regen Res. 2017 Oct;12(10):1687-1694. doi: 10.4103/1673-5374.217348.

Abstract

A previous study by our group found that inhibition of nischarin promotes neurite outgrowth and neuronal regeneration in Neuro-2a cells and primary cortical neurons. In recent years, more and more studies have shown that nanomaterials have good prospects in treatment of spinal cord injury. We proposed that small interfering RNA targeting nischarin (Nis-siRNA) delivered by polyethyleneimine-alginate (PEI-ALG) nanoparticles promoted motor function recovery in rats with spinal cord injury. Direct microinjection of 5 μL PEI-ALG/Nis-siRNA into the spinal cord lesion area of spinal cord injury rats was performed. From day 7 after surgery, Basso, Beattie and Bresnahan score was significantly higher in rats from the PEI-ALG/Nis-siRNA group compared with the spinal cord injury group and PEI-ALG/Control-siRNA group. On day 21 after injection, hematoxylin-eosin staining showed that the necrotic area was reduced in the PEI-ALG/Nis-siRNA group. Immunohistochemistry and western blot assay results confirmed successful inhibition of nischarin expression and increased protein expression of growth-associated protein-43 in the PEI-ALG/Nis-siRNA group. These findings suggest that a complex of PEI-ALG nanoparticles and Nis-siRNA effectively suppresses nischarin expression, induces expression of growth-associated protein-43, and accelerates motor function recovery after spinal cord injury.

摘要

我们团队之前的一项研究发现,抑制尼斯查林可促进Neuro-2a细胞和原代皮层神经元的神经突生长及神经元再生。近年来,越来越多的研究表明,纳米材料在脊髓损伤治疗方面具有良好前景。我们提出,由聚乙烯亚胺-海藻酸盐(PEI-ALG)纳米颗粒递送的靶向尼斯查林的小干扰RNA(Nis-siRNA)可促进脊髓损伤大鼠的运动功能恢复。将5 μL PEI-ALG/Nis-siRNA直接显微注射到脊髓损伤大鼠的脊髓损伤区域。术后第7天起,与脊髓损伤组和PEI-ALG/对照-siRNA组相比,PEI-ALG/Nis-siRNA组大鼠的Basso、Beattie和Bresnahan评分显著更高。注射后第21天,苏木精-伊红染色显示PEI-ALG/Nis-siRNA组的坏死区域减小。免疫组织化学和蛋白质印迹分析结果证实,PEI-ALG/Nis-siRNA组成功抑制了尼斯查林的表达,并增加了生长相关蛋白-43的蛋白表达。这些发现表明,PEI-ALG纳米颗粒与Nis-siRNA的复合物可有效抑制尼斯查林表达,诱导生长相关蛋白-43的表达,并加速脊髓损伤后的运动功能恢复。

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