Recombinant human erythropoietin (rh-EPO) has been shown to stimulate neurogenesis and angiogenesis, both of which play crucial roles in the repair of brain injuries. Previously, we observed that rh-EPO treatment effectively reduced brain damage and enhanced angiogenesis in a neonatal rat model of periventricular white matter damage (PWMD). The objective of this research is to investigate the specific mechanism through which rh-EPO regulates angiogenesis following PWMD in premature neonates. We conducted experiments utilizing a neonatal PWMD model. Following rh-EPO treatment, the levels of erythropoietin receptor (EPOR) were found to be increased in the damaged brain of rats. Although the total amount of extracellular signal-regulated kinase (ERK), a downstream protein in the EPO signaling pathway, remained unchanged, there was clear upregulation of phosphorylated ERK1 (p-ERK1) levels. The increase in levels of p-ERK1 was inhibited by an ERK kinase inhibitor, while the total amount of ERK remained unchanged. Conversely, the levels of EPOR were not affected by the inhibitor. Notably, the introduction of rh-EPO led to a significant increase in the frequency of angiogenesis-related cells and the expression levels of angiogenic factors. However, these effects were nullified when the ERK pathway was blocked. These findings indicate that rh-EPO enhances angiogenic responses through the EPOR-ERK1 pathway in a neonatal PWMD model.

中文翻译：

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在新生大鼠脑室周围白质损伤模型中，重组人促红细胞生成素通过 EPOR-ERK1 信号增强血管生成反应

重组人促红细胞生成素（rh-EPO）已被证明可以刺激神经发生和血管生成，这两者在脑损伤的修复中发挥着至关重要的作用。此前，我们观察到，在新生大鼠脑室周围白质损伤（PWMD）模型中，rh-EPO 治疗可有效减少脑损伤并增强血管生成。本研究的目的是探讨 rh-EPO 调节早产儿 PWMD 后血管生成的具体机制。我们利用新生儿 PWMD 模型进行了实验。rh-EPO治疗后，发现大鼠受损大脑中促红细胞生成素受体（EPOR）的水平增加。尽管细胞外信号调节激酶（ERK）（EPO信号通路下游蛋白）的总量保持不变，但磷酸化ERK1（p-ERK1）水平明显上调。p-ERK1水平的增加被ERK激酶抑制剂抑制，而ERK总量保持不变。相反，EPOR 的水平不受抑制剂的影响。值得注意的是，rh-EPO的引入导致血管生成相关细胞的频率和血管生成因子的表达水平显着增加。然而，当 ERK 通路被阻断时，这些作用就会消失。这些发现表明，在新生儿 PWMD 模型中，rh-EPO 通过 EPOR-ERK1 途径增强血管生成反应。