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促红细胞生成素通过降低C/EBP同源蛋白表达对实验性脊髓损伤的保护作用。

Protective effects of erythropoietin in experimental spinal cord injury by reducing the C/EBP-homologous protein expression.

作者信息

Hong Zhenghua, Hong Huaxing, Chen Haixiao, Wang Zhangfu, Hong Dun

机构信息

Kerman neuroscience research centre, Taizhou Hospital of Zhejiang Province, China.

出版信息

Neurol Res. 2012 Jan;34(1):85-90. doi: 10.1179/1743132811Y.0000000026.

Abstract

OBJECTIVES

Erythropoietin (EPO) is a variety of tissue-protective functions, including spinal cord. This study aimed to determine the neuron protective effect of erythropoietin on spinal cord injury (SCI) by assessing C/EBP-homologous protein (CHOP) in the development of a rat model of SCI.

METHODS

Sixty Sprague-Dawley rats were randomly assigned to three groups: sham-operation control group, SCI group, and EPO treatment group. By using a weight-drop contusion SCI model, the rats in the SCI group and EPO treatment group were killed at 1 and 7 days subsequently. The Basso, Beattie, and Bresnahan (BBB) scores were examined for locomotor function. Pathological changes were observed after hematoxylin-eosin (H&E) staining. The expression of CHOP was determined by immunohistochemical staining and RT-PCR analysis.

RESULTS

BBB scores showed more quick recovery in the erythropoietin treatment group than that in the SCI group (P < 0.01). Pathological changes also revealed a reduction in the volume of cavitations and more neurons regeneration in the EPO treatment rats than that of the SCI rats. The number of CHOP positive cells in the SCI group on day 1 and 7 days after SCI increased compared with the erythropoietin treatment group and sham-operation control group (P < 0.01). CHOP mRNA folds in sham-operation control rat from 1 to 7 days showed the same trend.

CONCLUSIONS

Endoplasmic reticulum (ER) stress was triggered at the early stage of SCI. Increased expression of CHOP can be found in the injured segment of the spinal cord after injury. EPO treatment could prevent pathological alterations from severe spinal cord injury by reducing expression of CHOP.

摘要

目的

促红细胞生成素(EPO)具有多种组织保护功能,包括对脊髓的保护。本研究旨在通过评估大鼠脊髓损伤(SCI)模型中C/EBP同源蛋白(CHOP)的表达,来确定促红细胞生成素对脊髓损伤的神经元保护作用。

方法

将60只Sprague-Dawley大鼠随机分为三组:假手术对照组、脊髓损伤组和促红细胞生成素治疗组。采用重物坠落撞击脊髓损伤模型,脊髓损伤组和促红细胞生成素治疗组的大鼠分别在术后1天和7天处死。通过Basso、Beattie和Bresnahan(BBB)评分评估运动功能。苏木精-伊红(H&E)染色后观察病理变化。采用免疫组织化学染色和RT-PCR分析测定CHOP的表达。

结果

促红细胞生成素治疗组的BBB评分恢复速度比脊髓损伤组更快(P < 0.01)。病理变化还显示,与脊髓损伤大鼠相比,促红细胞生成素治疗组大鼠的空洞体积减小,神经元再生更多。与促红细胞生成素治疗组和假手术对照组相比,脊髓损伤组术后1天和7天CHOP阳性细胞数量增加(P < 0.01)。假手术对照组大鼠1至7天的CHOP mRNA倍数呈现相同趋势。

结论

脊髓损伤早期会引发内质网(ER)应激。损伤后脊髓损伤节段CHOP表达增加。促红细胞生成素治疗可通过降低CHOP表达预防严重脊髓损伤的病理改变。

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