Li L, Guo J-D, Wang H-D, Shi Y-M, Yuan Y-L, Hou S-X
Department of Orthopaedics, The First Affiliated Hospital of General Hospital of the People's Liberation Army, Beijing 100048, China.
Department of Orthopaedics, The First Affiliated Hospital of General Hospital of the People's Liberation Army, Beijing 100048, China.
Neuroscience. 2015 Feb 12;286:27-36. doi: 10.1016/j.neuroscience.2014.11.037. Epub 2014 Nov 26.
Spinal cord injury (SCI) represents a severe health problem worldwide usually associated with severe disability and reduced quality of life. The aim of this work was to investigate the role of prohibitin 1 (PHB1) in the progression of SCI in rats. Firstly, we observed that expression of PHB1 was downregulated following SCI in rats. Then, we hypothesized that PHB1 overexpression by delivery of Ad-PHB1 could result in neuroprotection and promote functional recovery following SCI. Briefly, Wistar rats received a 35-g clip-compression injury and were administered Ad-PHB1 or Ad immediately following SCI. It was found that Ad-PHB1 administration significantly improved locomotor function and increased pain tolerance in rats with SCI. Furthermore, Ad-PHB1 administration following SCI attenuated axonal degradation and increased neuron sparing. Ad-PHB1 administration following SCI reduced apoptosis through inhibiting the Bcl-2/Bax/caspase-3 pathway. Ad-PHB1 administration following SCI suppressed endoplasmic reticulum stress, evidenced by reduced mRNA levels of CCAAT enhancer binding protein homologous protein, chaperone-ucose-regulated protein 78, and X-box protein 1. Ad-PHB1 administration following SCI restored mitochondrial adenosine triphosphate formation, reduced reactive oxygen species formation, and improved mitochondrial respiration rates. Finally, Ad-PHB1 administration following SCI activated downstream signals including phosphatidylinositol-3-kinase (PI3K)/Akt, extracellular signal-regulated kinase (ERK1/2), and nuclear factor-kappaB. These data indicate that the PHB1 plays an important role in the development of SCI and might provide a therapeutic target to promote recovery from SCI.
脊髓损伤（SCI）是全球范围内一个严重的健康问题，通常与严重残疾和生活质量下降相关。本研究的目的是探讨抑制素1（PHB1）在大鼠脊髓损伤进展中的作用。首先，我们观察到大鼠脊髓损伤后PHB1的表达下调。然后，我们假设通过递送Ad-PHB1来过表达PHB1可在脊髓损伤后产生神经保护作用并促进功能恢复。简要地说，Wistar大鼠接受35克夹压损伤，并在脊髓损伤后立即给予Ad-PHB1或Ad。结果发现，给予Ad-PHB1可显著改善脊髓损伤大鼠的运动功能并提高疼痛耐受性。此外，脊髓损伤后给予Ad-PHB1可减轻轴突退化并增加神经元保留。脊髓损伤后给予Ad-PHB1通过抑制Bcl-2/Bax/半胱天冬酶-3途径减少细胞凋亡。脊髓损伤后给予Ad-PHB1可抑制内质网应激，这可通过CCAAT增强子结合蛋白同源蛋白、伴侣蛋白-葡萄糖调节蛋白78和X盒蛋白1的mRNA水平降低来证明。脊髓损伤后给予Ad-PHB1可恢复线粒体三磷酸腺苷的形成，减少活性氧的形成，并提高线粒体呼吸速率。最后，脊髓损伤后给予Ad-PHB1可激活下游信号，包括磷脂酰肌醇-3-激酶（PI3K）/Akt、细胞外信号调节激酶（ERK1/2）和核因子-κB。这些数据表明，PHB1在脊髓损伤的发展中起重要作用，可能为促进脊髓损伤的恢复提供一个治疗靶点。
