The Study On The Ptotective Role Of Trimetazidine Against Myocardial Injury Of Pirarubicin And Adriamycin In Wistar Rats

Objective: To investigate the influence of trimetazidine in wistar rats that received pirarubicin (THP) and adriamycin (ADM) treatment, by analyzing the change rule of serum cardiac troponin I (cTnI) level and the pathological changes of myocardium observerd with microscope and transmission electron microscope , and evaluate the protection of myocardium injury of wistar rats after THP and ADM treatment with trimetazidine(TMZ).Methods: 32 wistar rats were randomly divided into 4 groups (8 cases each group):group A1(ADM+normal sodium group), group A2 (THP+normal sodium group),group B1(ADM+ TMZ group), group B2 (THP + TMZ group). ADM or THP was injected into intraperitoneal at the dosage of 2.5mg/kg, twice a week over a period of 4 weeks. From the third week,the rats in group A1, A2 were feed with normal sodium injections by intragastric administration with equal dosage with TMZ in group B1 and B2, the rats in group B1 and B2 were feed with TMZ (30mg/kg/d) by intragastric administration, once a day over a period of two weeks. All rats were treated with anesthesia by 10%chloraldurat on the third day after the last administration. Blood samples were taken from following respectively: before intragastric administration,before anesthesia and 30 min after anesthesia.The samples were centrifuged after they were put aside 30 min,and the blood serum were kept in -80°C refrigerator. Serum cTnI level was assay with MEIA methods. The pathological changes of myocardium were observed with microscope and transmission electron microscope.Results: (1) The changes of serum cTnI in four groups were statistically significant (P<0.05). Before intragastric administration,cTnI in group A1 were higher than in group A2 significanily ( P<0.05), the level of cTnI were no significant between group A1 and B1( P>0.05), between group A2 and B2 ( P>0.05) ;before anesthesia and after anesthesia,cTnI in group A2 and B1 were lower than in group A1 significanily ( P<0.05), cTnI in group B2 were lower than in group A2 significanily ( P<0.05). In group A1,A2,cTnI on before intragastric administration and before anaesthesia was no statistically significant (P>0.05),but the level of cTnI after anesthesia were higher than that before anaesthesia significanily ( P<0.05); In group B1,B2 ,the level of cTnI after anaesthesia were lower than that before intragastric administration significanily ( P<0.05), the level of cTnI after anaesthesia were higher than that before anaesthesia significanily ( P<0.05). (2) The pathological changes and myocardium ultramicro structure: in group A1, there were severely cellular degeneration and necrosis,muscular fibrils were breakaged,dissolved,the most mitochondrium were swelling , sarcoplasmic reticulum were dilated and vacuolus;in group B1, there were slightly cellular degeneration and necrosis,some mitochondrial were swelling, part of sarcoplasmic reticulum were dilateds ,the score of group A2 was lighter than that of group A1 (P<0.05) ;the changes in group B1 and B2 were more lighter than that in group A1 and A2(P<0.05).Conclusion: (1)THP and ADM treament can cause cardial injury, and THP induced cardial injury lighter than the ADM did. (2) Serum cTnI levels were decreased, cardial pathological score were decreased, and cardial ultrastructure was improved in wistar rats that received TMZ intervention. These resultes indicated that TMZ intervention both have cardial protective effect on cardial injury caused by THP and ADM treatment.