| Objective: Nicorandil,an opener of ATP sensitive K+ channel,has been proven to be an efficient drug for ischemic heart disease.Despite the fact that the protective effect of nicorandil for myocardial ischemia reperfusion injury(MIRI),has been verified in previous studies,the mechanism of such a protective effect has not been deeply understood.In the present study,the role of nicorandil in ameliorating MIRI was investigated.Methods: Seventy-five rats were randomly divided into five groups with fifteen rats in each group using a random numbers table.They were sham group,saline group and nicorandil A,B,C group.All rats in the saline and nicorandil groups were subjected to 30 minutes myocardial ischemia followed by 120 minutes reperfusion,via the surgical ligation of the left anterior descending coronary arteries(LAD)in the rats,and the rats in the sham group were not ligated.In the nicorandil A,B,C groups,0.2 mL nicorandil were administrated by the intravenous injection at the dose of 2.5 mg/kg,5.0 mg/kg,10.0 mg/kg at the onset of reperfusion.In the sham and saline groups,0.2 mL saline solution were administrated the same way as the nicorandil groups.At the end of reperfusion,blood sample was collected from the abdominal aorta for detecting the levels of CK-MB,cTnI,TNF-?,IL-1?,SOD,MDA,NO and ET-1.Hearts was removed for hemotoxylin and eosin(HE)staining and 2,3,5-triphenyltetramlium chloride(TTC)staining: HE staining was used for observing the pathologic changes of left ventricular;TTC staining for calculating the infarction size.Results: Compared with the sham group,the activities of CK-MB,cTnI,TNF-?,IL-1?,MDA,ET-1 contents decreased while the activities of NO,SOD increased in the saline and nicorandil groups(P < 0.05);The activities of CK-MB,cTnI,TNF-?,IL-1?,MDA,ET-1 contents decreased while the activities of NO,SOD increased in the nicorandil groups,when these were compared with the saline group(P < 0.05);Among the nicorandil groups,the levels of CK-MB,cTnI,TNF-?,IL-1?,MDA,ET-1 contents in the group B and C were lower than group A,the levels of NO,SOD in the group B and C were higher than group A(P < 0.05),but the difference between the group B and group C didnot have statistical significance(P > 0.05).TTC staining showed that infarction size was significant smaller in the nicorandil groups compared with that in the saline group(P < 0.05);Among the nicorandil groups,the infarction size in the group A was bigger than those in the group B and C(P < 0.05),but the difference between the group B and group C didnot have statistical significance(P >0.05).HE staining showed that cardiomyocytes arrangement was regular with clear margin and the horizontal grain was also legible in the sham group;In the saline group,cardiomyocytes arrangement was irregular,stripes of cardiac muscle fibers were significant edema,and abundant neutrophils were infiltrated into the myocardium.In addition,karyopyknosis was also observed;However,only mild cardiomyocytes irregularly arranged and edema were observed,and just few neutrophil infiltration were present in some areas of myocardium in the nicorandil groups.Conclusion: Pretreated with nicorandil,at the single dose before reperfusion,could attenuate MIRI,for it could reduce infarction size,inhibit oxidative stress and inflammatory outbreak,and preserve endothelial function;we also found that the 5.0 mg/kg was the optimistic dose of nicorandil in inhibiting MIRI.The protection mechanism of nicorandil for MIRI may be associated with its property of nitrate-like vasodilator effect. |
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