Erythropoietin-Induced Autophagy Protects Against Spinal Cord Injury and Improves Neurological Function via the Extracellular-Regulated Protein Kinase Signaling Pathway

被引:0
作者
Lin Zhong
Hui Zhang
Zheng-Fei Ding
Jian Li
Jin-Wei Lv
Zheng-Jun Pan
De-Xiang Xu
Zong-Sheng Yin
机构
[1] The First Affiliated Hospital of Anhui Medical University,Department of Orthopedics
[2] The Third Affiliated Hospital of Anhui Medical University,Department of Orthopedics
[3] Anhui Medical University,Department of Toxicology, School of Public Health
[4] Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes,undefined
来源
Molecular Neurobiology | 2020年 / 57卷
关键词
Extracellular-regulated protein kinases (ERK); Erythropoietin (EPO); Autophagy; Spinal cord injury (SCI);
D O I
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学科分类号
摘要
The objective of this study was to explore the neuroprotective molecular mechanisms of erythropoietin (EPO) in rats following spinal cord injury (SCI). First, a standard SCI model was established. After drug or saline treatment was administered, locomotor function was evaluated in rats using the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale. H&E, Nissl, and TUNEL staining were performed to assess the ratio of cavities, number of motor neurons, and apoptotic cells in the damaged area. The relative protein and mRNA expressions were examined using western blot and qRT-PCR analyses, and the inflammatory markers, axon special protein, and neuromuscular junctions (NMJs) were detected by immunofluorescence. Both doses of EPO notably improved locomotor function, but high-dose EPO was more effective than low-dose EPO. Moreover, EPO reduced the cavity ratio, cell apoptosis, and motor neuron loss in the damaged area, but enhanced the autophagy level and extracellular-regulated protein kinase (ERK) activity. Treatment with an ERK inhibitor significantly prevented the effect of EPO on SCI, and an activator mimicked the benefits of EPO. Further investigation revealed that EPO promoted SCI-induced autophagy via the ERK signaling pathway. EPO activates autophagy to promote locomotor function recovery in rats with SCI via the ERK signaling pathway.
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页码:3993 / 4006
页数:13
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