Cardioprotective effect of erythropoietin in rats with acute myocardial infarction through JNK pathway

Abstract

Objective: To explore the molecular mechanism of the cardioprotective effect of erythropoietin (EPO) in the rats with acute myocardial infarction (AMI) via the c-Jun N-terminal kinase (JNK) pathway.

Materials and methods: The rat AMI models were constructed and randomly divided into the EPO group, AMI group, and Sham group. At 2 weeks after successful modeling, the cardiac function-related indicators of rats were determined, and after the rats were sacrificed, the left ventricular weight (LVW) index was measured. The enzyme-linked immunosorbent assay (ELISA) and the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay were employed to determine the levels of the related serum inflammatory factors and myocardial apoptosis, respectively. The apoptosis and the expression levels of the JNK pathway-related messenger ribonucleic acids (mRNA) and proteins in the myocardial tissues of all groups of rats were determined via Real Time-Polymerase Chain Reaction (RT-PCR) and immunohistochemistry.

Results: After intervention with EPO, the EPO group had a substantially lower left ventricular end-diastolic pressure, but a remarkably higher left ventricular systolic pressure than the AMI group (p<0.05), and the LVW and LVW/body weight (BW) notably declined in the EPO group compared with those in AMI group (p<0.05). According to the ELISA results, the inflammatory factors were substantially raised in the AMI group compared with those in the other two groups (p<0.05) and significantly lowered after treatment with EPO (p<0.05). The TUNEL assay results revealed that EPO treatment could reverse the pathological changes in AMI to decrease the apoptosis to a large extent. It was detected via RT-PCR and immunohistochemistry that, compared with those in the Sham group, the expression level of the anti-apoptosis gene B-cell lymphoma 2 (Bcl-2) was substantially decreased, but the expression levels of pro-apoptosis gene Bcl-2 associated X protein (Bax) and the JNK pathway-related JNK and c-Jun were evidently elevated in the AMI group (p<0.05). Moreover, the expression level of Bcl-2 was remarkably raised (p<0.05) and the expression levels of Bax, JNK, and c-Jun remarkably declined (p<0.05) in the EPO group after intervention with EPO.

Conclusions: EPO can inhibit the inflammatory responses and decrease the myocardial apoptosis to protect the heart of the AMI rats, and its mechanism of action is related to the inhibition of the expression of the JNK pathway.