Expression And Mechanism Of MIR-208A And MIR-499 In Rat Myocardial Ischemia Reperfusion Injury And Ischemic Postconditioning

Background:Ischemic postconditioning (IPO) is an endogenous cardioprotective strategy which can protects the heart from ischemia-reperfusion (IR) injury. But the potential molecular mechanisms activated by IPO have not been fully disclosed. Hence, we sought to examine the potential involvement of miR-21、miR-208a、miR-499 and PDCD4、Caspase-3、α-MHC、β-MHC in IR and IPO rat heart.Methods:In the current study, Sprague-Dawley rats were randomly assigned into the following three groups:Sham group (n= 6), IR group (n =6), IPO group (n=6). Cardiac functional was evaluated by transthoracic echocardiography. The apoptotic percentage of cardiomyocytes was identified by AV/PI dual staining and flow cytometry analyses. The gene expression of miR-208a、miR-499、iR-21 and a-MHC、β-MHC in the area at risk were detected by quantitative real-time RT-PCR analysis. The expression of PDCD4, caspase-3 and α-MHC、β-MHC in the area at risk were detected by Western blot.Results:The results revealed that the left ventricular function was improved and apoptosis in cardiac myocytes were decreased in IPO. The expression of miR-208a was increased in IR group and decreased in IPO group. The expression of miR-499 was decreased in IR group and increased in IPO group. The expression of miR-21 was decreased in IR group and IPO group, but the expression difference in IR group and IPO group shows no statistical significance. The expressions of PDCD4 and caspase-3 were all increased in IR group and all decreased in IPO group. Meanwhile, the expression of β-MHC and β-MHC/a-MHC were increased in IR group and decreased in IPO group. The expression of a-MHC was not statistically different among the three groups.Conclusions:The left ventricular function was improved and the cardiomyocyte apoptosis was reduced by IPO-mediated protective effect against IR injury. MiR-499 seems to participate in IPO-mediated protective effect against IR injury by reducing cardiac cell apoptosis via the inhibition of PDCD4. The expression of miR-208a、β-MHC and β-MHC/a-MHC in IR was statistically increased; IPO could depresse the expression of miR-208a、β-MHC and β-MHC/a-MHC, which contribute to improvement of cardiac function to a certain extent.