Department of Anesthesiology, West China Second University Hospital, Sichuan University, No. 20, Section 3, South of Renmin Road, Chengdu, Sichuan, China.
Key Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of Education, Chengdu, Sichuan, China.
Biol Res. 2019 May 13;52(1):28. doi: 10.1186/s40659-019-0234-7.
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.
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).
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.
缺氧缺血性脑病（HIE）是围产期常见疾病，新生儿 HIE 的主要病因与胎儿宫内缺氧有关。促红细胞生成素（EPO）的衍生物碳氨化 EPO（CEPO）无促红细胞生成作用，但神经保护作用与 EPO 相似。先前的研究表明 CEPO 对中枢神经系统有潜在的益处。本研究旨在探讨 CEPO 在宫内 HIE 中神经元凋亡中的作用及其机制。
为验证我们的假设，我们通过阻断妊娠 Sprague-Dawley 大鼠双侧子宫卵巢动脉建立了宫内 HIE 模型。与 I/R 组相比，CEPO 组在 4、12、24 和 48 小时时神经元凋亡明显更低（P<0.05）。CEPO 在缺血再灌注后早期（0.5、4、8、12 和 24 小时）显著抑制 CC3 表达（P<0.05），并在 4、8、12 和 24 小时时上调 Bcl-2 表达，下调 Bax 表达（P<0.05）。
碳氨化 EPO 预处理抑制了脑内促凋亡蛋白 CC3 的表达，并调节了 Bcl-2/Bax 比值，从而减少了神经元凋亡，对宫内 HIE 具有保护作用。
