| Objective: Numerous studies have shown that ischemic postconditioning(IPostC) has obvious cardiac protection, diminishing the ischemia/reperfusion(I/R) injury. The reperfusion injury salvage kinase (RISK) pathway is animportant survival mechanism against reperfusion injury. Our previousobservation confirmed that the loss of cardioprotection by ischemicpostconditioning in middle-aged isolated rat hearts remained. The purpose ofthe study was to investigate whether age-related reduction of IPostC isassociated with the activation of extracellular regulated protein kinase1/2(ERK1/2) in isolated rat hearts of different ages.Method: Healthy male Sprague-Dawlay rats (n=72) were studied,including infancy rats (1-2months,150-200g), young rats (4-5months,300-350g), middle-aged rats (14-16months,550-650g). The rats of each agegroup were randomly divided into four treatment groups: I/R group, IPostCgroup, I/R+PD98059group and IPostC+PD98059group,6cases in eachgroup. PD98059was confirmed to inhibit up-regulation of ERK1/2. Rats wereanesthetized with sodium pentobarbital. The hearts were rapidly excised andperfused on a Langendorff apparatus with Krebs-Henseleit solution. Afterstabilization, hearts underwent30min of sustained global ischemia and120min of reperfusion. The hearts were subjected to6cycles of10seconds ofischemia and10seconds of reperfusion at the beginning of reperfusion inischemic postconditioning group. In the cases of PD98059, hearts wereperfused with PD98059(5×10-6M) for20min before complete reperfusion. Aballoon was inserted into the left ventricle, monitoring the cardiodynamicfunction (HR, LVDP, LVEDP,±dp/dtmax). The coronary effluent wasreserved at baseline and reperfusion1min,3min,5min,10min,20min,30min,60min,120min to assay the CK and LDH activity. The infarct size of the hearts was measured by TTC staining after2h reperfusion.Results:1Hemodynamic parameter1.1Infancy groupAt the end of baseline: there were no significant differences for LVDP,±dp/dtmax between I/R and IPostC and I/R+PD98059and IPostC+PD98059groups (P>0.05).At the end of2h reperfusion: the recovery rate of LVDP and±dp/dtmaxin IPostC group was significantly higher than that in I/R group (P<0.05); therecovery rate of LVDP and±dp/dtmax in IPostC+PD98059group wassignificantly lower than in IPostC group after inhibiting up-regulation ofERK1/2(P<0.05). Furthermore, there were no significant differences for therecovery rate of LVDP and±dp/dtmax between I/R and I/R+PD98059andIPostC+PD98059groups (P>0.05).1.2Young groupAt the end of baseline: there were no significant differences for LVDP,±dp/dtmax between I/R and IPostC and I/R+PD98059and IPostC+PD98059groups (P>0.05).At the end of2h reperfusion: the recovery rate of+dp/dtmax in IPostCgroup was significantly higher than that in I/R group (P<0.05); the recoveryrate of+dp/dtmax in IPostC+PD98059group was significantly lower than inIPostC group after inhibiting up-regulation of ERK1/2(P<0.05). Furthermore,there were no significant differences for the recovery rate of±dp/dtmaxbetween I/R and I/R+PD98059and IPostC+PD98059groups (P>0.05).1.3Middle-aged groupAt the end of baseline: there were no significant differences for LVDP,±dp/dtmax between I/R and IPostC and I/R+PD98059and IPostC+PD98059groups (P>0.05).At the end of2h reperfusion: there were no significant differences forthe recovery rate of LVDP and±dp/dtmax between I/R and IPostC andI/R+PD98059and IPostC+PD98059groups (P>0.05). 2Myocardial infarct size2.1Infancy groupThe infarct size of IPostC group was significantly smaller than that of I/Rgroup (P<0.05). The infarct size of IPostC+PD98059group was significantlylarger than that of IPostC group after inhibiting up-regulation of ERK1/2(P<0.05), but there were no significant differences for the infarct size betweenI/R and I/R+PD98059and IPostC+PD98059groups (P>0.05).2.2Young groupThe infarct size of IPostC group was significantly smaller than that of I/Rgroup (P<0.05). The infarct size of IPostC+PD98059group was significantlylarger than that of IPostC group after inhibiting up-regulation of ERK1/2(P<0.05), but there were no significant differences for the infarct size betweenI/R and I/R+PD98059and IPostC+PD98059groups (P>0.05).2.3Middle-aged groupThere were no significant differences for the infarct size between I/R andIPostC and I/R+PD98059and IPostC+PD98059groups (P>0.05).3The activity of creatine kinase (CK) and lactate dehydrogenase (LDH)3.1Infancy groupAt the end of baseline: there were no significant differences for theactivity of CK and LDH between I/R and IPostC and I/R+PD98059andIPostC+PD98059groups (P>0.05).During2h reperfusion: the activity of CK and LDH was significantlyincreased after sustained global ischemia; the peak appeared in first10min ofreperfusion, then gradually reduced. The increasing range of CK and LDHactivities in IPostC group was smaller than that in other treatment groups.The activity of CK in IPostC group was significantly lower than that inI/R group at reperfusion5-30min (P<0.05). The activity of CK in IPostC+PD98059group was significantly higher than that in IPostC group at reperfusion5-30min after inhibiting up-regulation of ERK1/2(P<0.05), but there were nosignificant differences for the activity of CK between I/R and I/R+PD98059and IPostC+PD98059groups at reperfusion (P>0.05). There were no significant differences for the activity of LDH betweenI/R and IPostC and I/R+PD98059and IPostC+PD98059groups (P>0.05).3.2Young groupAt the end of baseline: there were no significant differences for theactivity of CK and LDH between I/R and IPostC and I/R+PD98059andIPostC+PD98059groups (P>0.05).During2h reperfusion: the activity of CK and LDH was significantlyincreased after sustained global ischemia; the peak appeared in first5min ofreperfusion, then gradually reduced. The increasing range of CK and LDHactivities in IPostC group was smaller than in other treatment groups.The activity of CK in IPostC group was significantly lower than that inI/R group at reperfusion1-10min and30min (P<0.05). The activity of CK inIPostC+PD98059group was significantly higher than that in IPostC group atreperfusion1-10min and30min after inhibiting up-regulation of ERK1/2(P<0.05), but there were no significant differences for the activity of CKbetween I/R and I/R+PD98059and IPostC+PD98059groups at reperfusion(P>0.05).The activity of LDH in IPostC group was significantly lower than that inI/R group at reperfusion10-20min (P<0.05). The activity of LDH in IPostC+PD98059group was significantly higher than that in IPostC group atreperfusion10-20min after inhibiting up-regulation of ERK1/2(P<0.05), butthere were no significant differences for the activity of LDH between I/R andI/R+PD98059and IPostC+PD98059groups at reperfusion (P>0.05).3.3Middle-aged groupAt the end of baseline: there were no significant differences for theactivity of CK and LDH between I/R and IPostC and I/R+PD98059andIPostC+PD98059groups (P>0.05).During2h reperfusion: the activity of CK and LDH was significantlyincreased after sustained global ischemia; the peak appeared in first3min ofreperfusion, then gradually reduced.There were no significant differences for the activity of CK and LDH between I/R and IPostC and I/R+PD98059and IPostC+PD98059groups atreperfusion (P>0.05).Conclusions:1IPostC could recovery the abnormality of hemodynamics by ischemia/reperfusion injury for infancy and young rats to a certain extent, but thiscardio-protection was not obvious in the middle-aged rats.2IPostC could significantly reduce the infarct size by myocardialischemia/reperfusion injury for infancy and young rats, but IPostC could notsignificantly reduce the infarct size of middle-aged rats.3IPostC could significantly decrease the increased activity of CK andLDH by myocardial ischemia/reperfusion injury for infancy and young rats,but IPostC could not significantly decrease the increased activity of CK andLDH of middle-aged rats.4ERK1/2maybe participate in the cardioprotection of IPostC bybenefiting of hemodynamics, infarct size, CK and LDH activity.5The loss of cardioprotection by IPostC in middle-aged isolated rathearts maybe associated with the attenuated effect of ERK1/2related pathway. |
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