Experimental Study Of The Effect Of HIF-1a On Cardioprotection Of Remote Ischemic Postconditioning Against Ischemia/Reperfusion Injury In Vivo Rabbits

Objective:To observe the effect and mechanism of HIF-1α on cadioprotection of remoteischemic postconditioning induced by brief pulmonary ischemia reperfusion againstischemia/reperfusion injury in vivo rabbits.Metholds:Forty adult male rabbits,weight (2.1-2.5)kg, were randomly divided into fourgroups(each=10):①group control（group C）：rabbits underwent the same surgicalprocedures except that the suture passed under the left anterior descending branch（LAD）was not tightened；②ischemia/reperfusion group（group I/R）：rabbits weresubjected to30min of LAD occlusion followed by180min of reperfusion；③remoteischemic postconditioning group（group RIP）：the rabbits’ left pulmanary artery wasblocked5min followed by5min reperfusion while LAD was occluded20min andthen reperfused180min;④remote ischemic postconditioning withdimethyloxalylglycine(DMOG) group(group RIP+D): rabbits were pretreated with a20mg/kg DMOG24hours before RIP to stabilize HIF-1α. Blood samples wereharvested from internal jugular vein at three time points (before occlusion, beforereperfusion, at the end of test) respectively to analysis the concentration of creatinekinase (CK). Heart samples were collected for detection of myocardial infarct sizewith Evens blue and TTC method and detection of expression of HIF-1α withWestern-blot method and real time-PCR method.Results:There was no significant difference among four groups in the concentration ofCK before occlusion and before reperfusion (P>0.05). Before reperfusion, In additionto the group C, the concentration of CK in the other three groups were higher thanbefore. The concentration of CK in group I/R、group RIP and group RIP+D washigher than that in group C (P<0.01). But there was no significant difference amonggroup I/R、group RIP and group RIP+D in the concentration of CK. At the end of test,In addition to the group C, the concentration of CK in the other three groups were higher than before. The concentration of CK in group I/R was higher than that ingroup C (P<0.05). The concentration of CK in group RIP was lower than that ingroup I/R (P<0.05). The concentration of CK in group RIP+D was lower than that ingroup RIP (P<0.05).The myocardial infarct size of group I/R was significantly larger than that ofgroup C (P<0.01). The myocardial infarct size of group RIP was smaller than that ofgroup I/R (P<0.05). The myocardial infarct size of group RIP+D was smaller thanthat of group RIP (P<0.05).The expression of HIF-1α protein in group C was weak. The expression ofHIF-1α protein in group I/R was stronger than that in group C(P<0.05). Theexpression of HIF-1α protein in group RIP was stronger than that in group I/R(P<0.05). The expression of HIF-1α protein in group RIP+D was stronger than that ingroup RIP (P<0.05).The expression of HIF-1α mRNA in group I/R was stronger than that in groupC(P<0.05). The expression of HIF-1α mRNA in group RIP was stronger than that ingroup I/R (P<0.05). The expression of HIF-1α mRNA in group RIP+D was strongerthan that in group RIP (P<0.05).Conclusions:Remote ischemic postconditioning has a protective effect againstischemia-reperfusion injury. Remote ischemic postconditioning increased theexpression of HIF-1α, which may play a role in the cardioprotective effects of remotepostconditioning.