Protective effect of trimetazidine on myocardial ischemia reperfusion injury in ovariectomized rats and the effect on Fas and FasL gene expression

摘要

ABSTRACT Objective:To study the protective effect of trimetazidine on myocardial ischemia reperfusion injury in ovariectomized rats and the effect on Fas and FasL gene expression.Methods:Female Wistar rats were selected and divided into ovariectomized model group (OVX group), ovariectomized + ischemia reperfusion model group (OVX+I/R group) and ovariectomized + ischemia reperfusion + trimetazidine intervention group (OVX+I/R+TMZ group) (n=8), and the content of serum myocardial enzymes and structural proteins, hemodynamic indexes and the expression levels of apoptotic molecules and autophagy genes in myocardial tissue were determined.Results:Serum creatine kinase (CK) and isoenzyme (CK-MB), lactate dehydrogenase (LDH),α-hydroxybutyrate dehydrogenase (α-HBDH) content, troponin I (cTnI) and troponin T (cTnT) content as well as LVEDP level of OVX+I/R group were significantly higher than those of OVX group (P<0.05) while LVSP,+dp/dtmax and-dp/dtmax levels were significantly lower than those of OVX group (P<0.05), and serum CK, CK-MB, LDH,α-HBDH, cTnI and cTnT content as well as LVEDP level of OVX+I/R+TMZ group were significantly lower than those of OVX+I/R group (P<0.05) while LVSP,+dp/dtmax and-dp/dtmax levels were significantly higher than those of OVX+I/R group (P<0.05). Fas, FasL, Beclin-1 and P62 expression levels as well as LC3II/LC3I ratio in myocardial tissue of OVX+I/R group were significantly higher than those of OVX group (P<0.05), and Fas, FasL, Beclin-1 and P62 expression levels as well as LC3II/LC3I ratio in myocardial tissue of OVX+I/R+TMZ group were significantly lower than those of OVX+I/R group (P<0.05). Conclusions:Trimetazidine has protective effect on myocardial ischemia reperfusion injury in ovariectomized rats, and inhibiting cell apoptosis and cell autophagy mediated by Fas/FasL is the molecular mechanism for trimetazidine to play the protective role.