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Repair of Spinal Cord Injury by Inhibition of PLK4 Expression Through Local Delivery of siRNA-Loaded Nanoparticles
Journal of Molecular Neuroscience ( IF 3.1 ) Pub Date : 2021-09-01 , DOI: 10.1007/s12031-021-01871-1
Yingchu Gu 1 , Runze Zhang 1 , Bin Jiang 2 , Xin Xu 1 , Jun Jie Guan 3 , Xing Jie Jiang 3 , Yuan Zhou 4 , You Lang Zhou 5 , Xiangdong Chen 3
Affiliation  

Polo-like kinase 4 (PLK4) is one of the key regulators of centrosomal replication. However, its role and mechanism in spinal cord injury (SCI) are still unclear. The SCI model on rats was constructed and the expression and localization of PLK4 in the spinal cord are analyzed with Western blot and immunofluorescence, respectively. Then the specific siRNAs were encapsulated in nanoparticles for the inhibition of PLK4 expression. Afterward, the role of PLK4 on astrocytes was investigated by knocking down its expression in the primary astrocytes. Moreover, siRNA-loaded nanoparticles were injected into the injured spinal cord of rats, and the motor function recovery of rats after SCI was assessed using the Basso, Beattie, and Bresnahan (BBB) locomotor scale method. Notably, the siRNA-loaded nanoparticles effectively transfect primary astrocytes and significantly inhibit PLK4 expression, together with the expression of PCNA with significance. After treatment, restoration of the motor function following SCI was significantly improved in the PLK4 knockdown group compared with the control group. Therefore, we speculate that inhibition of Plk4 may inhibit the proliferation of astrocytes and decrease the inflammatory response mediated by astrocytes, so as to promote the functional recovery of SCI. In conclusion, inhibition of PLK4 expression via siRNA-loaded nanoparticles may be a potential treatment for SCI.



中文翻译:

通过局部递送载有 siRNA 的纳米颗粒抑制 PLK4 表达来修复脊髓损伤

Polo 样激酶 4 (PLK4) 是中心体复制的关键调节因子之一。然而,其在脊髓损伤(SCI)中的作用和机制仍不清楚。建立大鼠SCI模型,分别用Western blot和免疫荧光法分析PLK4在脊髓中的表达和定位。然后将特定的 siRNA 包裹在纳米颗粒中以抑制 PLK4 的表达。之后,通过降低其在原代星形胶质细胞中的表达来研究 PLK4 对星形胶质细胞的作用。此外,将载有siRNA的纳米颗粒注射到大鼠受伤的脊髓中,并使用Basso、Beattie和Bresnahan(BBB)运动量表方法评估SCI后大鼠的运动功能恢复情况。尤其,载有siRNA的纳米粒子有效转染原代星形胶质细胞并显着抑制PLK4的表达,同时PCNA的表达也具有重要意义。治疗后,与对照组相比,PLK4敲低组脊髓损伤后运动功能的恢复明显改善。因此,我们推测抑制Plk4可能会抑制星形胶质细胞的增殖,降低星形胶质细胞介导的炎症反应,从而促进SCI的功能恢复。总之,通过载有 siRNA 的纳米粒子抑制 PLK4 表达可能是 SCI 的潜在治疗方法。与对照组相比,PLK4 敲低组脊髓损伤后运动功能的恢复显着改善。因此,我们推测抑制Plk4可能会抑制星形胶质细胞的增殖,降低星形胶质细胞介导的炎症反应,从而促进SCI的功能恢复。总之,通过载有 siRNA 的纳米粒子抑制 PLK4 表达可能是 SCI 的潜在治疗方法。与对照组相比,PLK4 敲低组脊髓损伤后运动功能的恢复显着改善。因此,我们推测抑制Plk4可能会抑制星形胶质细胞的增殖,降低星形胶质细胞介导的炎症反应,从而促进SCI的功能恢复。总之,通过载有 siRNA 的纳米粒子抑制 PLK4 表达可能是 SCI 的潜在治疗方法。

更新日期:2021-09-02
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