Abstract:

Abstract:Objective  To explore the effects of trimetazidine on myocardial free radical injury induced by pirarubicin， and to clarify the protective effect and mechanism of trimetazidine on myocardial injury induced by pirarubicin.Methods 36 Wistar rats were randomly divided into pirarubicin group（n=13），trimetazidine intervention group（n=13） and control group （n=10）.The rats in pirarubicin group and trimetazidine intervention  group were injected with pirarubicin 2.5 mg/kg by the vena caudal once a week for 6 weeks.The rats in trimetazidine intervention  group were intragastricly infused with trimetazidine 5.4 mg/kg/d one day for 8 weeks before making the model. At the end of the experiment,the malonaldehyde (MDA) level，nitrogen oxide（NO） level，superoxide dismutase(SOD) activity，and nonprotein sulfhydryl (NPSH) level in  myocardium tissue were measured. The histological changes of myocardium tissue were detected by electron microscope. Results Compared with control group ,the levels of MDA and NO in pirarubicin group were increased（P<0.05），and the SOD activity and NPSH level in pirarubicin  group were decreased（P<0.05）.Compared with pirarubicin  group,the levels of MDA and  NO in trimetazidine intervention   group were decreased（P<0.05）， the SOD activity  and NPSH level in trimetazidine intervention  group were increased（P<0.05）.Under  electron microscope,the myocardiocytes of the rats in pirarubicin group showed irregular arrangement in sacromere structure,shrinkage in nuclear membrane,vacuolation in nuclear matrix,obvious mitochondria swelling,deposition of metachromatin throughout the nucleus,and an indistinct view of intercalated disc with isolation;while in trimetazidine intervention group the nucleus was round and nuclear membrane was indented,myofilament bundles were decreased slightly with a regular arrangement，intercalated disc oriented transversely with partial vague in cell junction structure,and mitochondria slightly swelled.Conclusion Trimetazidine has the protective effects on the damaged myocardiocytes caused by pirarubicin,and its mechanism may be related to reducing the production of free radicals and decreasing the injury of structures within the cells,such as the nucleus,mitochondria and intercalated disc.

Key words: trimetazidine, pirarubicin, myocardiocytes;mitochondria, free radicals