Mechanisms Of Erythropoietin In Protecting Cardiac Function In Diabetic Rats

Objective:To investigate the mechanisms of erythropoietin in improving cardiac function in diabetic rats.Methods:Forty male SD rats were randomly divided into control group,control-EPO group, diabetic group and diabetic-EPO group(n=10 for each).The diabetic model was induced by streptozotoein(STZ).In the control-EPO and diabetic-EPO group,rats were treated with 1000 IU�kg-1 EPO by subcutaneous injection once per week for twelve weeks.At the seventh day after the last administration, echocardiography was conducted. Blood samples from tail vein were collected for blood glucose and red blood cell numbers measurements. After rats were sacrificed,collecting myocardial tissues,quantitative real-time PCR(RT-PCR) was used to detect the mRNA level of GRP78?SERCA2a and EPOR, Western blot was used to detect the protein expression of GRP78?SERCA2a and EPOR.Results:1?After 12 weeks of STZ injection, body weight were greatly decreased in diabetic group compared with control group (P<0.01), compared with the diabetic group, body weight were increased noticeably in EPO-treated diabetic group (P<0.01).Blood glucose increased significantly and remained consistently higher in diabetic group and diabetic-EPO group than control group (P<0.01).TG?TC?LDL-C were significantly higher and HDL-C was significantly lower in diabetic group and diabetic-EPO group than control group(P< 0.01).No significantly difference was found in red blood cell count in four groups(P> 0.05).2?Ejection fraction(EF)was significantly decreased in diabetic group compared with control (P<0.01), EF was greatly increased in diabetic-EPO group compared with diabetic group (P<0.01).3?GRP78 mRNA expression was increased noticeably and SERCA2a? EPOR mRNA expression were decreased noticeably in diabetic group compared with control group(P<0.01);GRP78 mRNA expression was greatly decreased and SERCA2a?EPOR expression were greatly increased in diabetic-EPO group compared with diabetic group(P< 0.01).4?GRP78 protein expression was increased noticeably and SERCA2a?EPOR protein expression were decreased noticeably in diabetic group compared with control group(P< 0.01);GRP78 protein expression was greatly decreased and SERCA2a?EPOR protein expression were greatly increased in diabetic-EPO group compared with diabetic group (P< 0.01).Conclusion:1.EPO treatment can improve the cardiac function in diabetic rats.2.EPO can decrease GRP78 mRNA level and protein expression, suppress endoplasmic reticulum stress(ERS).3.EPO can increase SERCA2a?EPOR mRNA level and protein expression in diabetic rats.4.EPO treatment can improve the cardiac function in diabetic rats, which might be related to the inhibition of endoplasmic reticulum stress, up-regulating of the SERCA2a and EPOR expression.