Protective effect and mechanism of ischemic postconditioning in rats underwent myocardial ischemia/ reperfusion injury

Abstract

This study is designed to observe the effect of ischemic postconditioning in rats underwent acute myocardial ischemia/reperfusion injury and to investigate the related mechanism. A total of 30 SD rats were randomly divided into sham operation group (control group, n=10), ischemia/reperfusion group (IR group, n=10) and ischemic postconditioning group (PC group, n=10) based on random number table. Rats in IR group underwent 30 minutes myocardial ischemia by occlusion of the proximal portion of left anterior descending (LAD) coronary artery followed by 2 hours reperfusion. In control group, there was no IR intervention. In PC group, at the start of reperfusion, three cycles of 30 seconds reperfusion and 30 seconds LAD reocclusion preceded the 2 hours of reperfusion. The hemodynamic values were measured via a cannula inserted into the right common carotid artery.The area at risk was assessed by Evans blue staining and the infarct size as measured by TTC staining.Western blot and Real time PCR were respectively used to assess the expression of predicted target gene Bim and microRNA-214(miR-214) in the area at risk at the end of 2 hours reperfusion. (1) The hemodynamic monitoring in different groups: the left ventricular systolic pressure (LVSP), ±dp/dtmax, and heart rate of IR group and PC group were lower than those of control group, but left ventricular end-diastolic pressure (LVEDP) was higher than that of control group (all P<0.05). The LVSP and ±dp/dtmax of PC group were higher than those of IR group, and LVEDP was lower than that of IR group (all P<0.05). (2) Myocardial ischemia area and infarction range in different groups: there was no statistically difference in the proportion of area at risk (AAR) in left ventricle (LV) (AAR/LV) between PC group and IP group ((27.00 + 7.55) % vs. (26.67 + 11.68) %, P>0.05). The proportion of infarct size in the area at risk(IS/AAR) of PC group was lower than that of IR group((30.67±3.51)% vs. (48.67±4.62)%, P<0.05). (3) The expression of Bim protein in rats ischemic myocardial tissue in different groups: the expression of Bim protein in ischemic myocardial tissue of IR group was higher than that of control group (2.34±0.15 vs. 0.75±0.05, P<0.05), and that of PC group was lower than IR group (1.25±0.14 vs. 2.34±0.15, P<0.05). (4) The expression of of miR-214 in rats ischemic myocardial tissue in different groups: the expression of miR-214 of IR group was lower than that of control group(0.20±0.04 vs. 1.00, P<0.01), and that of PC group was higer than that of IR group (0.85±0.20 vs. 0.20±0.04, P<0.01). There was no statistically difference between PC group and control group (P>0.05). Postconditioning could significantly decrease the ischemia/reperfusion injury by reducing the infarct size and improve cardiac function in this in vivo rat model. The expression of Bim in postconditioning group is significantly depressed, which may play an important role in the protection process of postconditioning, and the downregulation of Bim might be mediated with the increase of miR-214 expression.