Experimental Studies Of Injured Effect Of Extracellular Heat Shock Protein 70 On The Myocardial Ischemia-reperfusion

The protective effect of intracelluar HSP70 on myocardial ischemia-reperfusion has been demonstrated in many experimnetal studies. Recently some studies have suggested that extracellcuar HSP70 could promote the expression and releasing of inflammatory factor, and the concentration of extracellcular HSP70 would increase when myocardium injuried(e.g:myocardial infraction, coronary artery bypass graft), and inflammatory response is very important part of myocardial ischemia-reperfusion injury. There are few reports on the change and effect of extracelluar HSP70 during myocardial ischemia-reperfusion. The present study is aimed to observe change of extracelluar HSP70 during ischemia-reperfusion, and research the effect and possible mechanisms of extracelluar HSP70 on ischemia-reperfusion injury.PartⅠStudy of the correlation between the concentration of extracelluar HSP70 and the degree of myocardial injury during ischemia-reperfusionObjective : To study changes of extracelluar HSP70 during acute myocardial ischemia-reperfusion, and the correlation between the changes and the degree of myocardial injury.Methods:Male KM Mice were randomly divided into two groups: sham operating group, ischemia-reperfusion (I/R) group. The ischemia-reperfusion heart model was established by ligating the left anterior descending branch of the coronary artery in I/R group, and not ligating in sham operating group. The concentration of serum HSP70 were detected at preoperation, 1 hour, 3 hours and 5 hours after reperfusion in both groups, and activities of serum creatine kinase(CK) at 1 hour, 3 hours and 5 hours after reperfusion in I/R group.Results:The serum HSP70 after reperfusion was significantly more than that before ischemia, and the increase reached the peak at 3 hours. Furthermore, serum HSP70 positively correlated with CK after reperfusion(r=0.879, p<0.001).Conclusion:The ischemia-reperfusion resulted into the increase of the concentration of extracellar HSP70, and this increase positively correlated with the degree of the ischemia-reperfusion injury.PartⅡEffect of extracellular HSP70 on the myocardial ischemia-reperfusion injuryObjective : To observe the effect of extracellular HSP70 on the myocardial ischemia-reperfusion injury in mice and study its possible mechanisms of action.Methods:Male KM Mice were randomly divided into three groups: sham operating group (A group), ischemia-reperfusion group (Bgroup), HSP70 group (C group), and the ischemia-reperfusion heart model was established by ligating the left anterior descending branch of the coronary artery except A group. And inject 0.2ml sterile normal saline, 0.2ml HSP70 by a catheter which was inserted into ascending aorta through right common carotid artery, when being reperfused. The activity of serum lactate dehydrogenase(LDH) and serum creatine kinase(CK), the activity of myeloperoxidase(MPO), the content of malondialdehyde(MDA) and expression of NF-κB in myocardial tissue were detected in every group at 5 hours after reperfusion.Results:The activities of CK, LDH and MPO, the content of MDA and expression of NF-κB in B group significantly increased compared with A group(p<0.05) ; but these items in C group also significantly increased compared with B group(p<0.05).Conclusion:Extracellular allogeneic HSP70 may aggravate myocardial reperfusion injury . The mechanisms may be related to the activation of NF-κB by the membrane receptor(TLR-4) and pro-inflammation response which results in local PMNs infiltrating and increasing reactive oxygen spieces and finally worsening inflammation response.