The Expression Of HO-1 And MCP-1 In Ischemic Reperfusion Myocardium And The Cardio-Protion Of Erythropoietin

Objective To observe the change of the expression of heme oxygenase-1and Monocyte chemoattractant protein-1 protein and mRNA in rat,s ischemic reperfusion(IR) myocardium,and to investigate the effect of erythropoietin(EPO) on the expression of MCP-1 and HO-1 of rats IR myocardial tissue and the change of myocardial ultrastructur, to explore the cardio-protective effects of EPO.Methods (1)30 adult male Sprague-Dawley rats were randomly separated into three groups: sham operation group (S group), operation group (O group) and heme oxygenase-1(HO-1) blocker ZnPP-Ⅸgroup (Z group). Ischemic reperfusion rat model was established in the experiments. The model rats were subjected to 45 min of myocardial ischemia by ligation of left anterior descending coronary artery followed by 180 min of reperfusion. The S group of rats were sham operated and injected intraperitoneally (ip) with saline. The O group underwent IR. The Z group were pretreated ip 24 hr before IR with ZnPP-IX(20μmol/kg). Specimens of the left ventricle were taken for determination of MCP-1 and HO-1 protein and mRNA by immunohistochemistry(IH) and RT-PCR.(2) 30 adult male Sprague-Dawley rats were randomly separated into three groups: operation group(O group),erythropoietin group(E group) and erythropoietin+ZnPP-Ⅸgroup (ZE group).The model was established as (1).The E group were pretreated ip 24 hr before IR with EPO(4000U/Kg). The ZE group were pretreated ip 24 hr before IR with EPO(4000U/Kg) and ZnPP-IX(20μmol/kg). Specimens of the left ventricle were taken for determination of MCP-1 and HO-1 protein and mRNA by IH and RT-PCR.The changes of myocardial ultrastructures were observed with transmission electronmicroscopy (TEM ).Results (1)Campared with F group, the expression of myocardial MCP-1 and HO-1 protein and mRNA increased significantly in O group and Z group (P< 0.01);The expression of HO-1 protein and mRNA was significantly reduced in Z group than that of O group (P<0.05) and the expression of MCP-1 protein and mRNA was significantly higher in Z group than that of O group (P<0.01); HO-1 and MCP-1 in O group and Z group were negative correlation(r=0.7474 and r=0.8123,P<0.01).⑵Campared with O group, The expression of HO-1 protein and mRNA was significantly increased(P<0.01 and P<0.05 ). But the expression of myocardial MCP-1 protein and mRNA reduced significantly in E group (P<0.05 ).The expression of HO-1 and MCP-1 protein and mRNA in ZE group were no difference campared with O group (P﹥0.05). The pretreatment with EPO markedly attenuated injury of the myocardial ultrastructur caused by IR.Conclusion The expression of HO-1 and MCP-1 protein and mRNA both increased significantly and seemed to be negative correlation in rats IR myocardium. The pretreatment with EPO significantly increased the expression of myocardial HO-1 and decreased the expression of myocardial MCP-1 and markedly attenuated injury of the myocardial ultrastructur caused by IR.