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首页> 外文期刊>Brain research >Overexpressing neuroglobin improves functional recovery by inhibiting neuronal apoptosis after spinal cord injury
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Overexpressing neuroglobin improves functional recovery by inhibiting neuronal apoptosis after spinal cord injury

机译：过度表达的神经球蛋白通过抑制脊髓损伤后神经元的凋亡来改善功能恢复

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摘要

The current study was performed to evaluate the mechanisms and therapeutic effects of overexpressing neuroglobin (Ngb) on spinal cord injury (SCI). Adeno-associated virus (AAV) was injected in the T12 section 7 days before SCI. Animals were randomly divided into four groups: a sham group, a vehicle group, an AAV-EGFP group and an AAV-Ngb group. Recovery of hind limb locomotor function was determined during the 3-week post operation period by the Basso, Beattie and Bresnahan locomotor rating scale. At 24 h after SCI and at the end of the study, the segments of spinal cord, centered with the lesion site were harvested for histopathological analysis. Immunofluorescence was performed using antibodies to recognize neuN in the lesion sections. At 24 h after SCI, the spinal cord tissue samples were removed to analyze tissue concentrations of superoxide dismutase (SOD) and malondialdehyde (MDA). Apoptotic cells were assessed using a terminal deoxynucleotidyl transferase, dUTP nick end labeling (TUNEL) kit. The expression of bcl-2, bax, cytochrome c, and cleaved caspase-3, were determined by Western blot assay and immunostaining analysis. The results showed that animals overexpressing Ngb had significantly greater recovery of locomotor function, less neuronal loss and fewer apoptotic cells. In addition, overexpressing Ngb significantly increased bcl-2 expression and SOD level, decreased bax expression, attenuated the release of cytochrome c from mitochondria to the cytosol fraction, and reduced the activity of caspase-3 and MDA level after SCI. These findings suggest, that overexpressing Ngb can significantly improve the recovery of locomotor function. This neuroprotective effect may be associated with theinhibition of neural apoptosis via the mitochondrial pathway.
机译：进行本研究以评估过表达神经球蛋白（Ngb）对脊髓损伤（SCI）的机制和治疗效果。在SCI前7天，在T12区域注射腺相关病毒（AAV）。将动物随机分为四组：假手术组，媒介物组，AAV-EGFP组和AAV-Ngb组。在术后3周内，通过Basso，Beattie和Bresnahan运动评分标准来确定后肢运动功能的恢复。在脊髓损伤后24小时和研究结束时，收集以病变部位为中心的脊髓节段进行组织病理学分析。使用抗体进行免疫荧光识别病变部位的neuN。 SCI后24小时，取出脊髓组织样品以分析超氧化物歧化酶（SOD）和丙二醛（MDA）的组织浓度。使用末端脱氧核苷酸转移酶，dUTP缺口末端标记（TUNEL）试剂盒评估凋亡细胞。通过蛋白质印迹分析和免疫染色分析确定bcl-2，bax，细胞色素c和裂解的caspase-3的表达。结果表明，过表达Ngb的动物的运动功能恢复明显更高，神经元损失更少，凋亡细胞更少。此外，过表达Ngb显着增加bcl-2表达和SOD水平，降低bax表达，减弱细胞色素c从线粒体到胞质溶胶的释放，并降低SCI后caspase-3活性和MDA水平。这些发现表明，过表达Ngb可以显着改善运动功能的恢复。这种神经保护作用可能与通过线粒体途径抑制神经细胞凋亡有关。

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