| Objective: At present,there is a lack of effective measures for the treatment of ischemia-reperfusion.In this study,we established an acute myocardial ischemia-reperfusion reperfusion(I/R)model in rats to observe the effects of nicorandil preconditioning on microvascular endothelial function and myocardial,and to explore its mechanism,and to provide theoretical basis and treatment ideas for clinical prevention and treatment of MIRI.Methods:60 Wistar rats were randomly divided into Sham operation(SO)group,ischemia reperfusion(I/R)group and nicorandil(Nic)group,There are 20 in each group.Each group was randomly divided into two groups:group ? and group ?,to check experimental indexes.Nic group received nicorandil injection(5 mg/kg)via tail vein 30 minutes before operation.SO and I/R group received the same amount of saline 30 minutes before operation.During the operation,I/R group and Nic group were used to establish the model of myocardial ischemia for 30 minutes and reperfusion for 120 minutes.SO group was used as control group,only under coronary artery left anterior decending artery(LAD)puncture line without ligation.The color of ventricular wall and the changes of electrocardiogram(ECG)were observed to determine whether the model of myocardial ischemia and reperfusion was successful.After 120 minutes of reperfusion,each group measure the concentrations of nitric oxide(NO),endothelin(ET-1),group ? measure the total superoxide dismutase(T-SOD)and malondialdehyde malondialdehyde(MDA)and observation the microvascular endothelial cells under electron microscope,group ? use Evans blue and TTC staining,to measure the area of myocardial ischemia and myocardial infarction.Results:1.The comparison of serum NO and ET-1 levels:NO level in I/R groupwas significantly lower than that in SO group(P<0.05),NO level in Nic group was significantly higher than that in I/R group(P<0.05),NO level in Nic group was not different from that in SO group(P=0.06).In terms of ET-1 level,both I/R and Nic groups were significantly higher than SO group(P<0.05),Nic group significantly lower than I/R group(P<0.05).2.The comparison of changes of microvascular endothelial cells under transmission electron microscope:In SO group,the microvascular lumen is regular and unobstructed,the endothelial cell structure is normal,the nucleus of cell is normal,and the endothelial cell is connected closely.In I/R group,the microvascular injury is obvious,the microvascular lumen is severely shriveled,and the shape is irregular.The basement membrane was uneven,loose connection between endothelial cells,enlargement of the inner nucleus of endothelial cell.In Nic group,most of the microvascular lumen is more patency,no obvious stenosis,endothelial cell damage is slight,slightly swollen nucleus can be seen.3.The comparison of T-SOD and MDA levels in myocardium: The content of T-SOD in group I/R was lower than that in group SO(P<0.05).The decrease of T-SOD in group I/R was more significant than that in group Nic(P<0.05).In the level of MDA,both group I/R and group Nic were higher than those in group SO(P<0.05),and the level of group Nic was significantly lower than that of group I/R(P<0.05).4.Compared with the I/R group,the infarct area in the I/R group was decreased significantly(P<0.05),and the risk area was similar to that in the Nic group(P>0.05).Conclution:1.Ischemia reperfusion can damage the structure and function of microvascular endothelial cells.2.Nicorandil pretreatment can improve the structure and function of microvascular endothelium during reperfusion,alleviate oxidative stress,and enhance the antioxidant ability of the body3.Nicorandil pretreatment can effectively prevent reperfusion injury,reduce myocardial infarction area. |
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