[Effects of erythropoietin on cardiomyocyte apoptosis and endoplasmic reticulum stress-related proteins in neonatal rats with asphyxia].

Abstract

OBJECTIVE:

To study the effects of erythropoietin (EPO) on cardiomyocyte apoptosis and endoplasmic reticulum stress (ERS)-related proteins, glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP), in neonatal rats with asphyxia.

METHODS:

A total of 120 newborn Sprague-Dawley rats (7 days old) were randomly divided into sham-operated (n=40), asphyxia (n=40) and EPO-treated asphyxia groups (n=40). A neonatal rat model of normobaric asphyxia was established in the asphyxia and EPO-treated asphyxia groups. The rats in the EPO-treated asphyxia group received intraperitoneal injection of recombinant human erythropoietin (500 U/mL) immediately after the model was established, while the other two groups received the same volume of normal saline (0.9%). Heart blood and myocardial tissue samples were collected from 8 rats in each group at 2, 6, 12, 24 or 48 hours after the model was established. Serum creatine kinase (CK) and lactate dehydrogenase (LDH) levels were measured; cardiomyocyte apoptosis was evaluated, and expression of myocardial GRP78 and CHOP was measured.

RESULTS:

Compared with the sham-operated and EPO-treated asphyxia groups, the asphyxia group had significantly increased serum CK and LDH levels, number of apoptotic cells, and expression of myocardial GRP78 and CHOP at each time point (P<0.01), and all the indices were significantly higher in the EPO-treated asphyxia group than in the sham-operated group (P<0.01). At 24 hours after asphyxia, the expression of myocardial CHOP was positively correlated with the myocardial apoptosis index (r=0.944, P<0.01).

CONCLUSIONS:

EPO exerts a protective effect on the myocardium of neonatal rats with hypoxic-ischemic injury by regulating ERS-related proteins GRP78 and CHOP and reducing cardiomyocyte apoptosis.

• Authors: Li-Jia Wan, Xing-Heng Wu
• Journal: Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics (Zhongguo Dang Dai Er Ke Za Zhi) Vol. 15 Issue 10 Pg. 890-5 (Oct 2013) ISSN: 1008-8830 [Print] China
• PMID: 24131844 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ddit3 protein, rat
• Endoplasmic Reticulum Chaperone BiP
• GRP78 protein, rat
• HSPA5 protein, human
• Heat-Shock Proteins
• Erythropoietin
• Transcription Factor CHOP
• L-Lactate Dehydrogenase
• Creatine Kinase

Topics

• Animals
• Animals, Newborn
• Apoptosis (drug effects)
• Asphyxia Neonatorum (drug therapy, pathology)
• Creatine Kinase (blood)
• Endoplasmic Reticulum Chaperone BiP
• Endoplasmic Reticulum Stress (physiology)
• Erythropoietin (pharmacology)
• Heat-Shock Proteins (analysis)
• L-Lactate Dehydrogenase (blood)
• Myocytes, Cardiac (drug effects, pathology)
• Rats
• Rats, Sprague-Dawley
• Transcription Factor CHOP (analysis)