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目的探讨重组人促红细胞生成素(rEPO)对脑室周围白质软化(PVL)新生大鼠的神经保护作用。方法新生5 d(P5)SD大鼠96只随机分成3-硝基丙酸(3-NPA)脑内注射损伤组(3-NPA组)、rEPO治疗组(rEPO组)和假手术对照组(PBS组),其中rEPO组于脑损伤前0.5 h予rEPO腹腔注射(50 U/10 g体质量),3组于术后不同时间点行HE染色和免疫荧光标记,计算髓鞘磷脂蛋白(MBP)和神经生长相关蛋白(GAP-43)阳性细胞数,术后24 d(P29)行神经行为学测定。结果 HE染色显示3-NPA组P7时皮质下及脑室周围白质出现不同程度疏松及液化灶,P14出现脑室扩大;P7时,PBS组和rEPO组注射部位周围脑组织疏松液化,P14、P12时未见明显脑室扩大。P7、P8时,3组脑室周围白质中均有MBP阳性细胞表达,P14、P30时,3-NPA组阳性细胞数低于PBS组和rEPO组(Pa<0.05);P30时,3-NPA组GAP-43阳性细胞较rEPO组和PBS组减少(Pa<0.05);神经行为学测定显示3-NPA组较PBS组和rEPO组反应差(P<0.05)。结论 rEPO可减轻新生大鼠脑白质损伤、促进神经生长修复,发挥远期神经保护作用。
Objective To investigate the neuroprotective effect of recombinant human erythropoietin (rEPO) on neonatal rats with periventricular leukomalacia (PVL). Methods 96 neonatal 5-day-old SD rats were randomly divided into 3-NPA group (3-NPA group), rEPO group (rEPO group) and sham operation control group PBS group). The rEPO group was intraperitoneally injected with rEPO (50 U / 10 g body weight) 0.5 h before brain injury, and the three groups were subjected to HE staining and immunofluorescence labeling at different time points to calculate myelin phospholipid protein (MBP ) And nerve growth-related protein (GAP-43) positive cells, neurological behavior was measured 24 days after operation (P29). Results Hematoxylin-eosin staining showed that there were different levels of loose and liquefied lesions in P7 subcutaneous and periventricular white matter in 3-NPA group and enlarged ventricles in P14. At P7, the brain tissue loosely liquefied around the injection site in PBS group and rEPO group, See clearly ventricular enlargement. P7 and P8, MBP-positive cells were expressed in the periventricular white matter of all three groups. At P14 and P30, the number of positive cells in 3-NPA group was lower than that in PBS group and rEPO group (P <0.05) GAP-43 positive cells decreased compared with rEPO group and PBS group (P <0.05). Neuro-behavioral assay showed that 3-NPA group had less reaction than PBS group and rEPO group (P <0.05). Conclusions rEPO can reduce the white matter damage of neonatal rats, promote the growth and repair of nerve cells and exert long-term neuroprotective effect.