摘要
目的探讨大鼠局灶性脑梗死后，重组人促红细胞生成素(RhEPO)对少突胶质细胞相关的神经胶质抗原2型硫酸软骨素糖蛋白(NG2)、Nogo受体作用蛋白(LINGO-1)、髓鞘碱性蛋白(MBP)和髓磷脂相关糖蛋白(MAG)表达情况的作用，通过以上蛋白的表达阐述RhEPO对于神经胶质细胞保护作用的机制。方法36只大鼠分为RhEPO治疗组(脑缺血后分别于30min、3h、6h、12h及24h加入RhEPO3000U·kg-1·d-1腹腔注射，连用7d，30只)、盐水对照组(于术后30min给予腹腔注射生理盐水，7d，每天1次，6只)，利用神经功能缺损评分(mNSS)及免疫组织化学法检测相关蛋白NG2、MAG、MBP及LINGO-1表达情况。结果脑缺血后7d，RhEPO治疗组较盐水对照组mNSS明显降低(P<0．05)，以30min及3h给药组更为明显(P<0．01)。RhEPO治疗各组较盐水对照组NG2阳性细胞数量明显增加，LINGO-1阳性细胞数目减少，差异有统计学意义(P<0．05)，30min及3h组更显著(P<0．01)。较盐水对照组，各实验给药组MBP蛋白表达缺失程度减轻，而MAG蛋白表达减少，差异具有统计学意义(P<0．05)，30min给药组更显著(P<0．01)。结论脑缺血后，RhEPO促进NG2阳性细胞增殖，抑制LINGO-1、MAG蛋白的表达及髓鞘的脱失，进一步保护神经元提高神经功能恢复。早期应用，效果明显。
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 significandy 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 < O. 05 ), with a dramatic decrease observed at 30 min and 3 h (P < O. O1 ). 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 < O. 05 ) , especially at 30 rain ( P < 0. O1 ). 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.
出处
《中华病理学杂志》
CAS
CSCD
北大核心
2015年第5期323-328,共6页
Chinese Journal of Pathology
基金
黑龙江省留学归国基金(LC2013C30)
哈尔滨医科大学附属第一医院留学归国基金(2012LX04)
