Effect of carbamylated erythropoietin on neuronal apoptosis in fetal rats during intrauterine hypoxic-ischemic encephalopathy

Abstract 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 erythropoieti...

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Main Authors: Min Diao, Yi Qu, Hui Liu, Yushan Ma, Xuemei Lin
Format: Article
Language:English
Published: BMC 2019-05-01
Series:Biological Research
Subjects:
Online Access:http://link.springer.com/article/10.1186/s40659-019-0234-7
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author Min Diao
Yi Qu
Hui Liu
Yushan Ma
Xuemei Lin
author_facet Min Diao
Yi Qu
Hui Liu
Yushan Ma
Xuemei Lin
author_sort Min Diao
collection DOAJ
description Abstract 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.
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spelling doaj.art-4928baf6d5104cc8829feef5a8439b1a2022-12-21T18:44:48ZengBMCBiological Research0717-62872019-05-0152111110.1186/s40659-019-0234-7Effect of carbamylated erythropoietin on neuronal apoptosis in fetal rats during intrauterine hypoxic-ischemic encephalopathyMin Diao0Yi Qu1Hui Liu2Yushan Ma3Xuemei Lin4Department of Anesthesiology, West China Second University Hospital, Sichuan UniversityKey Laboratory of Birth Defects and Related Diseases of Women and Children, Sichuan University, Ministry of EducationDepartment of Anesthesiology, West China Second University Hospital, Sichuan UniversityDepartment of Anesthesiology, West China Second University Hospital, Sichuan UniversityDepartment of Anesthesiology, West China Second University Hospital, Sichuan UniversityAbstract 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.http://link.springer.com/article/10.1186/s40659-019-0234-7Carbamylated erythropoietinNeuronal apoptosisIntrauterine hypoxic-ischemic encephalopathy
spellingShingle Min Diao
Yi Qu
Hui Liu
Yushan Ma
Xuemei Lin
Effect of carbamylated erythropoietin on neuronal apoptosis in fetal rats during intrauterine hypoxic-ischemic encephalopathy
Biological Research
Carbamylated erythropoietin
Neuronal apoptosis
Intrauterine hypoxic-ischemic encephalopathy
title Effect of carbamylated erythropoietin on neuronal apoptosis in fetal rats during intrauterine hypoxic-ischemic encephalopathy
title_full Effect of carbamylated erythropoietin on neuronal apoptosis in fetal rats during intrauterine hypoxic-ischemic encephalopathy
title_fullStr Effect of carbamylated erythropoietin on neuronal apoptosis in fetal rats during intrauterine hypoxic-ischemic encephalopathy
title_full_unstemmed Effect of carbamylated erythropoietin on neuronal apoptosis in fetal rats during intrauterine hypoxic-ischemic encephalopathy
title_short Effect of carbamylated erythropoietin on neuronal apoptosis in fetal rats during intrauterine hypoxic-ischemic encephalopathy
title_sort effect of carbamylated erythropoietin on neuronal apoptosis in fetal rats during intrauterine hypoxic ischemic encephalopathy
topic Carbamylated erythropoietin
Neuronal apoptosis
Intrauterine hypoxic-ischemic encephalopathy
url http://link.springer.com/article/10.1186/s40659-019-0234-7
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