Effect Of Irbesartan On Expression Of Vascuolar Cell Adhesion Molecule-1 (VCAM-1) And Intercellular Adhesion Molecule-1 (ICAM-1) In The Myocardial Ischemia-reperfusion Areas Of Rabbits

OBJECTIVE:The aim was to explore the effects provided by irbesartan on acute myocardia ischemial-reperfusion injury and on the expression of ICAM-1 and VCAM-1 in the myocardial ischemia-reperfusion areas.METHODS:Twenty-four male New Zealand White rabbits(weighing 1800-2000g were used)were randomly divided into three groups:sham,control and treatment.Each involves eight rabbits.The rabbits were fed daily with ordinary food. Each animal in treated group was additionally fed daily with irbesartan(5mg.kg-1.day-1).Two weeks later,the model of I/R was established.In the sham group,the heart was exposed after the chest had been oponed, but coronary artery was not ligated. In the other two groups,the rabbits were subjected to 60 min of left main coronary occlusion,followed by 360 min of reperfusion. Electrocardiogram was recorded before ischemia,during ischemia and reperfusion respectively in every rabbit of model. The blood(4ml) was taken from vein in very rabbit ears before the chest was opened.The blood(5ml) was extracted from right atrium at the time of 450 min after the chest had been opened in the sham group,but in the other two groups at 360 min after reperfusion.Serum levels of the MB isoenzyme of creatine kinase(CK-MB) were measured.The rabbit was killed at 450 min after the chest had been opened in the sham group,but at 360 min after reperfusion in the other two groups.The tissue samples removed from I/R areas. The samples were embedded in paraffin wax after fixed with 10% neutral solution and disposed with routine histological methods.They were examined by light microscopy after staining with hematoxylin and eosin(HE).Also,the expressions of ICAM-1 and VCAM-1 were investigated by employing immunohistochemical SP method and computer image analysis in the tissue samples.RESULTS:In the sham group, the S—T segments were not obviously abnormal changes. In the treated group, The elevated S—T segments decreased markely during two hours of reperfusion (P<0.05,vs control group). But all in the treated group or in the control group there were "QS" at 360 min of reperfusion,no difference.Both in the treated group and in the control group the levels of CK-MB were significantly increased(P<0.01,vs sham group),however the levels of CK-MB of the treated group were evidently decreased compared with control group(P<0.01).As compared with the control group,the damage degree of myocytes and neutrophil infiltration were greatly reduced in the treated group(P<0.01; P<0.01),and got more lower In the sham group. Expression of VCAM-1 and ICAM-1 in the I/R areas both in the control group and in the treated group were greatly regulated(P<0.01,P<0.01,vs sham group).And the expressions of above in vestigated index were significantly different between the control group and the treated group,in the former, the expressions of VCAM-1 and ICAM-1 tended to be more strong(P<0.01,P<0.01).CONCLUSION:These data suggest that (1)I/R markely induced expression of VCAM-1 and ICAM-1 in the I/R areas .(2) irbesartan can greatly depressed expression of VCAM-1 and ICAM-1 in the I/R areas.(3) irbesartan exerts an important protective effect against myocardial I/R injury of rabbits by depressing expression of VCAM-1 and ICAM-1.