| ObjectiveIn this study,I/R model of rats was established by coronary artery ligation to observe the expression of calcium overload related protein PLB and SERCA2 a and the intervention of trimetazidine,to further investigate the role of TMZ in myocardial ischemia-reperfusion injury.MethodNinety adult male SD rats were randomly divided into three groups: sham operation(SH)group,myocardial ischemia-reperfusion injury(I / R)group,and myocardial ischemia-reperfusion injury + trimetazidine(I / R + TMZ)group,each consisting of 30 rats.Ten rats from each group were randomly sacrificed at immediate,2,4 weeks,and then the morphology of the myocardium was observed by HE staining,the m RNA expression levels of SERCA2 a and PLB were detected by real-time PCR,and the protein expression levels of SERCA2 a,p-plb,and PLB were detected by Western blot.Statistical methods were applied to analyze whether the changes of the above indicators were statistically significant.Result1.HE stainingIn sham group,cardiomyocytes were arranged neatly and tightly,morphologically intact,and stained uniformly,with almost no inflammatory cell infiltration.Compared with the sham group,the I / R group showed obvious disarrangement of cardiomyocytes,obvious swelling of cells,obvious fragmentation of myocardial fibers,and a large number of inflammatory cell infiltration were seen.Compared with the I / R group,the arrangement of cardiomyocytes in the I / R + TMZ group was relatively compact and neat,and slight edema of the cells was seen,no obvious fracture of the myocardial fibers was observed,and a small number of inflammatory cell infiltration was seen.Compared with tissues harvested at week 2from the I / R + TMZ group,those from the I / R + TMZ group showed better morphological recovery,more complete arrangement of cardiomyocytes,less edema,and less obvious inflammatory cell infiltration at week 4 than those from the I / R +TMZ group.2.Expression levels of SERCA2 a,PLB m RNA and protein,as well as p-PLB proteinWithin group comparison: there was no statistical significance in the expression of SERCA2 a m RNA and protein as well as p-plb protein between samples taken immediately,2 and 4 weeks after sham procedure(P > 0.05).The expression levels of SERCA2 a m RNA and protein as well as p-plb protein were the lowest in the I / R group when samples were taken at 2 weeks compared with the immediate and 4weeks(P < 0.05);However,the expression levels of SERCA2 a m RNA and protein as well as p-plb protein in all groups with immediate retrieval were not statistically significant(P > 0.05).The expression levels of SERCA2 a m RNA and protein as well as p-plb protein were the lowest in the I / R + TMZ group when samples were taken at week 2 and were lower than those obtained immediately and at week 4(P < 0.05),whereas the highest expression levels of SERCA2 a m RNA and protein and p-plb protein were obtained at week 4 and the differences were statistically significant(P <0.05).There was no statistical significance in PLB m RNA and protein expression in all periods(P > 0.05).Comparisons between groups: compared with the sham group,the m RNA and protein expression levels of SERCA2 a,p-plb decreased at all time points in the I / R group,with significant differences(P < 0.05);Compared with the sham group,SERCA2 a m RNA and protein and p-plb protein expression levels decreased at all time phases in the I / R group,with significant differences(P < 0.05);Compared with the sham group,the expression levels of SERCA2 a m RNA and protein as well as p-plb protein were decreased in the I / R +TMZ group immediately after sacri fi CE and week 2,with statistical signi fi cance(P< 0.05).However,the expression levels of SERCA2 a m RNA and protein as well as p-plb protein in the I / R + TMZ group harvested at week 4 were not significantly different from those in the sham group(P > 0.05).Compared with the immediate post-i / R group,the expression levels of SERCA2 a m RNA and protein and p-plb protein in the immediate post-i / R + TMZ group were not statistically significant(P >0.05),and the expression levels of SERCA2 a m RNA and protein and p-plb protein in the immediate post-i / R + TMZ group were increased at weeks 2 and 4,with significant differences(P < 0.05).PLB m RNA and protein expression in all groups were not statistically significant(P > 0.05).Conclusion1.SERCA2 a and p-plb expression are reduced after myocardial ischemia-reperfusion injury,we speculate that myocardial I / R may be associated with reduced SERCA2 a expression as well as reduced p-plb expression inhibiting SERCA2 a activity and reducing calcium uptake by the sarcoplasmic reticulum,thereby leading to intracellular calcium overload.2.Trimetazidine can increase the expression of SERCA2 a and p-PLB to protect myocardium.It is speculated that trimetazidine may improve SERCA2a’s uptake of calcium ions in the cytoplasm by releasing the inhibition of SERCA2 a by phosphorylation of PLB and increasing the expression of SERCA2 a,so as to maintain the calcium homeostasis and protect the myocardium. |
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