Protective Effect And Mechanisms Of MiR-484 On Myocardial Ischemia-reper-fusion Injury In Rats

ObjectiveTo reveal the myocardial protective effect and its possible mechanism of miR-484 on myocardial ischemia-reperfusion(I/R)injury.MethodsRats model of myocardial I/R injury was established based on sham operation group(Con)group,Ischemia-reperfusion(I/R)group,miR group and I/R-negative control(IR-C)group in which forty male SD rats were selected and randomly divided.Hemodynamic measurement were performed before surgery and 2 hours after reperfusion to confirm successful model construction;HE staining was used to observe pathological changes in myocardial tissue;Ultrastructural changes were observed under transmission electron microscopy;The expression levels of IL-6,TNF-α and IL-1β was evaluated using enzyme linked immunosorbent assay(ELISA);TUNEL assay was performed to detect myocardial cellular apoptosis in ischemic region;The expression of Caspase-3 and Caspase-9 in myocardial cells were detected by Western blot.Results(1)Hemodynamic results showed that compared with the Con group after2 h reperfusion,LVEDV and LVESV in both I/R group and IR-C group were significantly higher than before,while LVEF、LVFS were obviously lower than before(P<0.05);LVEDV and LVESV in miR group were significantly higher thanthose in I/R and IR-C groups,while LVEF and LVFS were significantly lower than those groups(P<0.05).(2)The expression of miR-484 in the I/R and IR-C groups were obviously down-regulated compared with the Con group(P<0.05);The expression of miR-484 was obviously up-regulated in miR group compared with the I/R and IR-C groups(P<0.05).(3)Compared with the Con group,the expression levels of IL-6,TNF-αand IL-1β in cardic myocytes of the I/R group and IR-C group were up-regulated(P<0.05);compared with the I/R and IR-C groups,the expression levels of the above-mentioned inflammation factors in miR group were down-regulated(P<0.05).(4)Compared with the Con group,the myocardial apoptosis index in the ischemic region of the I/R and IR-C groups was significantly increased,while the mitochondrial membrane potential was significantly reduced(P<0.05);compared with the I/R and IR-C groups,the apoptotic index was significantly reduced,while the mitochondrial membrane potential was significantly increased in miR group(P<0.05).(5)Compared with the Con group,caspase-3 and caspase-9 protein expression levels in the I/R and IR-C groups were significantly increased(P<0.05);compared with the I/R and IR-C groups,the caspase-3 and caspase-9protein expression levels were significantly down-regulated in miR group(P<0.05).ConclusionThe mechanisms of miR-484 can reduce the damage of cardiomyocytes during I/R injury is as following aspects:(1)Mi R-484 reduced the expression of IL-6,TNF-α and IL-1β in MI/R,alleviate MI/R injury.(2)Mi R-484 might alleviate the decreasing of mitochondrial membrane potential in MI/R and protects myocardial cells from I/R injury.(3)Mi R-484 reduces caspase-3 and caspase-9expression during cardiomyocyte apoptosis,thereby miR-484 protectedmyocardial cells from I/R injury.