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重组人促红细胞生成素对脑梗死少突胶质细胞的保护作用

[Protective effects of recombinant human erythropoietin on oligodendrocyte after cerebral infarction].

作者信息

Hua Wei, Wu He, Zhou Min, Liu Wei, Zhu Jiyuan, Gu Yunhe, Zhang Zhen, Wang Hongda, Liu Qi, Qi Jiping

机构信息

Department of Pathology, the First Affiliated Hospital of Harbin Medical University, Harbin 150001, China.

Department of Pathology, the First Affiliated Hospital of Harbin Medical University, Harbin 150001, China; E-mail:

出版信息

Zhonghua Bing Li Xue Za Zhi. 2015 May;44(5):323-8.

Abstract

OBJECTIVE

To study biological effect of recombinant human erythropoietin (RhEPO) on the expression of oligodendrocyte in the neuron glia antigen 2(NG2), Nogo receptor-interacting protein 1(LINGO-1), myelin basic protein (MBP) and myelin associated glycoprotein (MAG), and to explore the protective mechanism of RhEPO for oligodendrocyte after cerebral infarction.

METHODS

Experimental rats were randomly divided into the treatment group (RhEPO at a dose of 3 000 U/kg) or saline control group. Both groups received intraperitoneal injection of RhEPO after cerebral ischemia in 30 min, 3 h, 6 h, 12 h and 24 h, which was administered daily for 7 days. The modified neurological severity score (mNSS) and histology were analyzed, and immunohistochemistry was used to detect the protein expression of NG2, MAG, MBP and LINGO-1.

RESULTS

The overall mNSS of RhEPO treatment group significantly decreased compared with the saline control group on the seventh day after cerebral infarction (P<0.05). Such treatment effect was more obvious in the treatment group at 30 min and 3 h (P<0.01). Compared with the saline control group, the numbers of NG2 positive cells increased in RhEPO treatment group. In contrast, the expression of LINGO-1 protein significantly decreased (P<0.05), with a dramatic decrease observed at 30 min and 3 h (P<0.01). However, the expression of MBP protein decreased more significantly in saline control group, while the level of the MAG protein expression increased. The differences were statistically significant (P<0.05), especially at 30 min (P<0.01).

CONCLUSIONS

After cerebral ischemia, RhEPO promotes the proliferation of NG2 positive cells, and inhibits the expression of LINGO-1 and MAG proteins. RhEPO improves the proliferation and differentiation of oligodendrocyte precursor cells, which in turn protects neuronal function, particularly at the early phase of ischemia.

摘要

目的

研究重组人促红细胞生成素(RhEPO)对少突胶质细胞中神经胶质抗原2(NG2)、Nogo受体相互作用蛋白1(LINGO-1)、髓鞘碱性蛋白(MBP)和髓鞘相关糖蛋白(MAG)表达的生物学效应,探讨RhEPO对脑梗死少突胶质细胞的保护机制。

方法

将实验大鼠随机分为治疗组(3000 U/kg的RhEPO)和生理盐水对照组。两组在脑缺血后30分钟、3小时、6小时、12小时和24小时进行腹腔注射RhEPO,每日给药1次,共7天。分析改良神经功能缺损评分(mNSS)和组织学情况,采用免疫组化法检测NG2、MAG、MBP和LINGO-1的蛋白表达。

结果

脑梗死第7天,RhEPO治疗组的总体mNSS较生理盐水对照组显著降低(P<0.05)。在30分钟和3小时时治疗组的这种治疗效果更明显(P<0.01)。与生理盐水对照组相比,RhEPO治疗组中NG2阳性细胞数量增加。相反,LINGO-1蛋白表达显著降低(P<0.05),在30分钟和3小时时显著下降(P<0.01)。然而,生理盐水对照组中MBP蛋白表达下降更显著,而MAG蛋白表达水平升高。差异具有统计学意义(P<0.05),尤其是在30分钟时(P<0.01)。

结论

脑缺血后,RhEPO促进NG2阳性细胞增殖,抑制LINGO-1和MAG蛋白表达。RhEPO改善少突胶质细胞前体细胞的增殖和分化,进而保护神经元功能,尤其是在缺血早期。

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