Efficacy Of Trimetazidine On Myocardium And Skeletal Muscle Energy Metabolism In Rats With Heart Failure After Myocardial Infarction

Objective:(1)To investigate the effects of trimetazidine on activity of mitochondrial respiratory chain complex I,II,III and IV of myocardial and skeletal muscle in rat.(2)To investigate the effects of trimetazidine on UCP3 expression of myocardial and skeletal muscle in rat.Methods: 8 week old male SD rats were randomly divided into five groups: sham operation group,model group,low dose,middle dose and high dose of trimetazidine group,and 6 rats in each group.Myocardial infarction was induced by ligation of left anterior descending coronary artery in model group.4 weeks later,those rats were further divided into model group,low dose of trimetazidine group(10 mg/kg),middle dose group(20 mg/kg)and high dose group(40 mg/kg).Model group was not given drugs,and other steps were the same as those in the model group except that the coronary artery was not ligated.Elisa was used to detect the levels of serum NT-pro BNP in rats.The mitochondria of myocardium and skeletal muscle were extracted,and activity of mitochondrial respiratory chain complex I,II,III and IV was detected by colorimetric method.Expression of UCP3 in myocardium and skeletal muscle tissue was detected by Western blot.Results:(1)The results of echocardiography showed that the left ventricular enlargement,the left ventricular anterior wall thinning,and the left ventricular ejection fraction and shortening fraction in the model group were significantly reduced(P<0.05),indicating that the myocardial infarction model was successfully established in rats.(2)Serum NT-pro BNP in model group were significantly higher than that of sham operation group(P < 0.05).Serum NT-pro BNP in low dose group,middle dose group and high dose of trimetazidine group were significantly lower than those in model group(P < 0.05),and showed obvious dose dependency.The results showed that Trimetazidine can improve cardiac function,and showed obvious dose dependency.(3)The activity of mitochondrial respiratory chain complex I,III and IV in myocardium and skeletal muscle tissue in model group were significantly lower than that in sham operation group(P < 0.05).The activity of mitochondrial respiratory chain complex I,III and IV in myocardium and skeletal muscle tissue in low dose group,middle dose group and high dose of trimetazidine group were significantly higher than that in model group(P < 0.05),and showed obvious dose dependency.However,there was no significant difference in the activity of mitochondrial respiratory chain complex II(P > 0.05)in the myocardium and skeletal muscle tissue in all groups.(4)Expression of UCP in myocardium and skeletal muscle tissue in model group,low dose group and middle dose of trimetazidine group were significantly higher than that in sham operation group(P < 0.05).Expression of UCP in myocardium and skeletal muscle tissue in middle dose group and high dose of trimetazidine group were significantly lower than that in model group(P < 0.05),and showed obvious dose dependency.Conclusions: With heart failure after myocardial infarction in rats,the levels of serum NT-pro BNP were significantly increased,Trimetazidine can improve cardiac function and reduce NT-pro BNP;and myocardium and skeletal muscle energy metabolism disorder.activity of mitochondrial respiratory chain complex I,III and IV significantly decreased,and expression of UCP3 was increased significantly.Trimetazidine may down-regulate the expression of the of UCP3 to increase the activity of mitochondrial respiratory chain complex I,III and IV,further to promote the formation of ATP,ultimately improving myocardial and skeletal muscle function.