Effect Of Erythropoietin Activating Epo-Epor Signaling Pathway On Improving Cardiac Function In Diabetic Rats

Objective: To investigate the effect of the erythropoietin-activating EPO-EPOR signalling pathway on improving cardiac function in diabetic rats.Methods: The rats were randomly divided into the normal control group, the diabetes group and the diabetes + EPO intervention group, with 10 rats in each group. The diabetic rats model was established. The rats in the diabetes + EPO intervention group were given a subcutaneous injection of 1000IU/kg EPO and the normal control group and the diabetes group were given subcutaneous injections of normal saline of equal volume once a week for 12 consecutive weeks. Echocardiography was used to determine the heart to body weight ratio, left ventricular end-diastolic diameter (LVDd), ejection fraction (EF) and left ventricular end-systolic diameter (LVDs) in rats. The levels of blood lipids (glycerin trilaurate [TG]), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), blood glucose content and blood routine red blood cell (RBC) were measured by the Hitachi automatic biochemical analyser, the GOD-PAP method and the blood routine detector JHF7-3000, respectively. The expression of the glucose-regulated protein 78 (GRP78), the sarcoplasmic reticulum Ca2+-ATP enzyme (SERCA2a) and the EPOR mRNA in the left ventricular myocardium of the rats was detected by an RT-PCR assay. The expression levels of GRP78, SERCA2a and EPOR proteins were detected by a western blot assay and the immunohistochemistry method.Results: The EF and LVDD values of rats in the diabetes group were significantly lower than those of the normal control group (P<0.01), and the heart to body weight ratio was markedly higher than that of the normal control group (P<0.01). There was no statistically significant difference in LVDS between the diabetes group and the normal control group (P>0.05). The EF value of rats in the diabetes + EPO intervention group was significantly higher than that in the diabetes group, and the LVDS and LVDD values and heart to body weight ratio were remarkably lower than those in the diabetes group (P<0.01). The body weight and HDL-C levels of the rats in the diabetes group were significantly lower than those in the control group, while the levels of blood glucose, TG, TC and LDL-C were remarkably higher than those in the control group (P<0.01). There was no statistically significant difference in the RBC level between the diabetes group and the control group (P>0.05). Moreover, the weight of rats in the diabetes + EPO intervention group was significantly higher than that in the diabetes group, and there was no statistically significant difference in blood lipid, blood glucose and RBC levels compared with the diabetes group (P>0.05). The expression of GRP78 mRNA in the diabetes group was markedly higher than that in the control group (P<0.01), and the expression of the SERCA2a, EPOR mRNA in the diabetes group was significantly lower than that in the control group (P<0.01). Besides, the expression of the GRP78 mRNA in the diabetes + EPO group was significantly lower than that in the diabetes group (P<0.01), and the expression of the SERCA2a, EPOR mRNA in the diabetes group was obviously higher than that in the diabetes group (P<0.01). The expression of the GRP78 protein in the diabetes group was significantly higher than that in the control group (P<0.01), and the expression of the SERCA2a, EPOR protein in the diabetes group was remarkably lower than that in the control group (P<0.01). Moreover, the expression of the GRP78 protein in the diabetes + EPO group was significantly lower than that in the diabetes group (P<0.01), and the expression of the SERCA2a, EPO protein in the diabetes group was significantly higher than that in the diabetes group (P<0.01).Conclusion: EPO can effectively improve cardiac function in rats, which may be due to the activation of the EPO-EPOR signalling pathway by reducing the stress response of the myocardial endoplasmic reticulum, thus leading to the increased expression of the SERCA2a and EPOR protein and playing a protective role in the heart.