| ObjectiveTo investigate the expression of high mobility group box-B1 (HMGB1) in rat myocardium after ischemia-reperfusion injury; and to research the protective effects of simvastatin pretreatment on myocardial ischemic reperfusion injury (MIRI) in rat myocardium.MethodsSixty healthy adult Wistar rats were randomly divided into four groups: the sham operation group(n=10), the ischemia-reperfusion model group(IR group,n=10),the low dose of simvastatin pretreated group(SIM-L group,n=10) and the high dose of simvastatin pretreated group(SIM-H group,n=10), respectively.Six days before the model was established, each rat of SIM-L group was administered with 10 mg?kg-1?d-1 simvastatin intragastrically, and the dose of SIM-H group was 20mg?kg-1?d-1, while the other rats were treated with physiological saline at same dose daily;After six days pretreatment, every rat was operated and the left anterior descending artery(LAD) was ligated to establish the model except for the rats of sham group were treated with sutures only passing under the LAD , without ligation, After Ischemia for 30 minutes and reperfusion for 12 hours, 2ml blood was collected from jugular vein to detect the expression of HMGB1 and cTnI by the methods of ELISA, then all the rats were executed and myocardial samples were taken to investigate the expression of HMGB1 protein using immunohistochemical methods, The histological changes were observed by light-microscopy with the use of HE stain..Results(1)The expression of HMGB1 and cTnI in serum of I/R group were both significantly higher than those of the sham group(P <0.01). HMGB1 protein expressed more in IR group than that in sham group (P<0.01).(2)The serum HMGB1 and cTnI in SIM-L group were lower than those in the I/R group(P<0.01), but still higher than that of the sham group(P<0.01). And the expression of HMGB1 protein in myocardiumof the SIM-L group decreased significantly than that of the I/R group (P<0.01)。(3)In SIM-H group, the serum HMGB1 and cTnI were greater lower than those of the SIM-H group (P<0.05),but they were higher than that of the sham group (P<0.01). The myocardial expression of HMGB1 protein in SIM-H group was lower than that of the SIM-L group(P>0.05.(4)The correlation analysis indicated that the expression of HMGB1 in serum was positively correlated with cTnI. (r =0.694, P<0.01).(5)Morphological changes was observed under light microscope after the use of HE staining: The appearance of cardiac myocyte in sham group was about nomal; part of myocardial cell nuclear had then undergone karorrhexis and karyolysis, myocardial cell appeared edema, myocardial fiber enlargerd significantly ,with disordered, inflammatory cells were examined infiltration in interstitium; compared with the I/R group, the degree of myocardial injury and inflammatory cells infiltration was decreased and cardiac myocyte arranged orderliness in groups of Sim-L and Sim-H, especially in Sim-H group.Conclusions(1). The study suggests that HMGB1 may play an important role in the process of myocardial I/R injury.(2).Simvastatin pretreatment can effectively decrease the injury of myocardium after ischemia/reperfusion, this indicated that it had protective action in myocardial ischemia/reperfusion progress.(3).Simvastatin pretreatment can decrease the expression of HMGB1,this maybe one of its mechanisms of anti-MIRI function. |
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