| Objective and background:ischemical reperfusion injury of limb is a common pathophysiological phenomenon clinically.Ischemia of the limbs is a unavoidable occurrence during peripheral vasculai surgery, insult of limbs,thrombogenesis,abdominal aneurysm surgery, replantation of extremities,peripheral vascular injury or crushing syndrome.Recent studies have shown that limb IR can trigger a systemic inflammatory response syndrome(SIRS).It causes not only local tissue injury,but also remote organs dysfunction including heart,liver,lung,kindy and small intestine.clinical studies suggest that the heart is at high risk in the setting of sirs.the mechanism of acute myocardial injury following limb IR is very complicated,up to now,not completely elucidated yet.a great quantity of study indicate that severe ischemical reperfusion injury of limb can induce irritable high blood pressure,arrhythmia,myocardial ischemia and cardia insufficiency,heme oxygenase-1 is a ubiquitous stress protein and is induced in many cell types by various stimuli.the this stimuli all can induce oxidative stress.The protective effects of HO-1 is very important via its antiinflammatory,antiapoptotic,antiproliferative, and antioxidant properties,as well as its effects on the immune response. In the present study,we have established the model of bilateral hindlimb ischemia and reperfusion in rats by using a tourniquet.To explain the mechanism of myocardial injury and autoprotection by observing pathologic change of myocardium,the mechanism of oxidative stress and the expression of HO-1mRNA..our experiment is divided into two parts:Firstly,we explore the role of oxidative stress in the myocardial injury following the limb ischemical reperfusion injury by observing change of myocardium.secondly,we are to ascertain the protective effects of endogenous HO-lon the myocardial injury during the limb ischemical reperfusion.Method:we have established the model of bilateral hindlimb ischemia and reperfusion in rats by using a tourniquet.the experimental rats were divided to 7 groups randomly.Igroup:Normal group;Ⅱgroup:a group of animals were subjected to suffer ischemic 4h and reperfusion 2h,Ⅲgroup:ischemic 4h and reperfusion 4h;Ⅳgroup:ischemic 4h and reperfusion 6h;Ⅴgroup:ischemic 4h and reperfusion 8h;Ⅵgroup: ischemic 4h and reperfusion 16h;Ⅶgroup:ischemic 4h and reperfusion24h.the first part:to observe pathological change of myocardium by using light microscope,to measure the content of MDA,T-SOD and MPO in the serum and myocardium.;the second part:to detect the expression of HO-1mRNA by using RT-PCR.Result:After reperfusion 4h,myocardial cells were engorged, Vascular engorgement and Small spatium intermusculares were widen obviously,a bulk of akaryocyte and nucleated cells were observed in the spatium intermusculare,above-mentioned change were lessen following reperfusion 24h.To compare with normal group normal,plasma and myocardium MDA:The levels of MDA,MPO in plasma and the levels of MDA,MPO in myocardium were significantly increased in all groups of IR(P＜0.01),and the myocardial and plasma levels of SOD were markedly decreased(P＜0.01).However,the plasma levels of MDA and MPO and the myocardial level of MDA achieved to high-peak after reperfusion for 4h,then they decreased,while,the myocardial level of MPO reach to high-peak following IR for 6h,the plasma level of SOD reach to nadir after IR for 4h,but the myocardial level of SOD reach to nadir following IR for 8h.limb IR can induce to up-regulation of HO-1mRNA,compared to grounp normal:the expression of HO-1 was not significant change after IR2h(P＞0.05).and it is markedly increased after IR4h,and up to peak after IR16h(P＜0.01).Conclusion:Limb IR can induce myocardial injury.the injury is the most serious during 4-6h after reperfusion.The mechanism may be involved in the activating of neutrophil and inflammatory cytokines,excess oxidative stress,the imbalance of oxidant-antioxidant system,organism have the mechanism of autoprotection,the up-regulation of endogenous HO-1 may play an important role in myocardial injury following limb IR.
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