BACKGROUND Hypoxic-ischemic encephalopathy (HIE) is a common disease that occurs during the perinatal period. The primary cause of neonatal HIE is related to fetal intrauterine anoxia. Carbamylated erythropoietin (CEPO), a derivative of erythropoietin (EPO), does not exert any erythropoietic effect; however, the neuroprotective effects resemble those of EPO. Previous studies have shown the potential benefits of CEPO on the central nervous system. The present study aimed to investigate the role of CEPO in neuronal apoptosis during intrauterine HIE and the underlying mechanisms. RESULTS To validate our hypothesis, we established an intrauterine HIE model by occluding the bilateral utero-ovarian arteries of pregnant Sprague-Dawley rats. Compared to the I/R group, neuronal apoptosis in the CEPO group was significantly lower at 4, 12, 24, and 48 h (P < 0.05). CEPO significantly inhibited CC3 expression (P < 0.05) during the early-stages after ischemia-reperfusion (0.5, 4, 8, 12 and 24 h), upregulated Bcl-2 expression, and downregulated Bax expression at 4, 8, 12, and 24 h (P < 0.05). CONCLUSIONS Carbamylated erythropoietin pretreatment inhibited the expression of proapoptotic protein CC3 in brain and regulated the Bcl-2/Bax ratio, resulting in reduced neuronal apoptosis and thus resulting in a protective effect on intrauterine HIE.

中文翻译：

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氨基甲酸酯化的促红细胞生成素对宫内缺氧缺血性脑病期间胎鼠神经元凋亡的影响。

背景技术缺氧缺血性脑病（HIE）是围生期期间发生的常见疾病。新生儿HIE的主要原因与胎儿宫内缺氧有关。氨基甲酸酯化的促红细胞生成素（CEPO）是促红细胞生成素（EPO）的衍生物，不发挥任何促红细胞作用。但是，神经保护作用类似于EPO。先前的研究表明，CEPO对中枢神经系统具有潜在的益处。本研究旨在探讨CEPO在宫内HIE期间神经元凋亡中的作用及其潜在机制。结果为了验证我们的假设，我们通过闭塞怀孕的Sprague-Dawley大鼠的双侧子宫-卵巢动脉建立了子宫内HIE模型。与I / R组相比，CEPO组的神经元凋亡在4、12、24，48小时（P <0.05）。在缺血再灌注后的早期（0.5、4、8、12和24 h），CEPO显着抑制CC3表达（P <0.05），在4、8、12和12时，Bcl-2表达上调，Bax表达下调。 24小时（P <0.05）。结论氨基甲酸酯化的促红细胞生成素预处理可抑制脑中促凋亡蛋白CC3的表达并调节Bcl-2 / Bax比值，从而减少神经元凋亡，从而对子宫内HIE产生保护作用。