| Background and Objective: Adriamycin (ADM ) is a kind of anthracene medicine which used widely and effectively in clinic for the treatment of solid tumor and neoplastic hematologic disorder. However, the cardiac toxicity induced by dose accumulation of adriamycin restrict its application for a long time. The mechanisms about the cardiac toxicity include oxidative stress, mitochondrion damage, calcium overload, apoptosis of the myocardium cell and so on. As a result, how to lessen the cardiac toxicity induced by ADM became important in this investigation territory. Recently,people made great progression in the cordis protective agent which use to oppose the cardiac toxicity caused by ADM. However the effective of these drugs used in clinic is not so good as peoples' expections. It is necessary to develop a new drug which has a better therapeutic effect for the adverse effect caused by ADM. Thrombopoietin(TPO)is a glycoprotein which promote the proliferation and differentiation of hemopoietic stem/progenitor cell and megakaryocyte. It also increases the production of platelets. For the past few years,people realized the effectiveness of TPO on non- hematopoietic system. It has been proved that TPO protect the heart which damaged by the ADM by conflicted the apoptosis of the myocardial cell. Up to now,people still don't know whether the other mechanisms exist. In our investigation, we hope to validate the potective effect of TPO again by determining myocardial damage marker in serum and pathological change. At same time, we try to use the antioxidation mechanism to explain on cardiotoxicity.Methods: 32 Wistar rats were randomized into four groups. There were 8 rats in each group. ADM group was given adriamycin by intraperitoneal injection at the dosage of 20mg/kg once at 0 day. ADM+TPOL(Low-dose group) and ADM +TPOH (High-dose group) were injected ADM,which dosage,application and time were similar to ADM group. At same time, TPO was injected into intraperitoneal at the dosage of 10 ug/kg or 30ug/kg three times before one day(-1day)and after one day(+1day),two day(+2day) when they were given ADM. Control group was given N.S at the dosage of 10ml/kg at -1day,0day,+1day,+3day, respectivly. ALL rats were anesthetized by 2% pentobarbital to gained specimens at +5day. ELISA was used to detect CK-MB and cTnI content of serum in the rats. The ultrastructure change of cadiocyte was observed by the electron microscope. We use 8-hydroxy-2′- deoxyguanosine (8-OHdG)monoclonal antibody to detect 8-OHdG in rats' myocardium tissue demaged by ADM through the immunohistochemistry stain method. IPP6.0 software was used to detect IOD in three regions from one slice and calculate the 8-OHdG index.Results: The energy of CK-MB and cTNI in control group was lower obviously than the other groups. The energy of CK-MB and cTNI in the groups which were given TPO was lower obviously than the ADM group. There was no significant statistics difference between the ADM+TPOL group and ADM+ TPOH group. Under electron microscope, the ultrastructure of myocard tissue in the ADM group was damaged more severely than the control group. The cellular swelling of myocardium, breakage and solution of actin filament and swelling of chondriosome were observed. Construction of cardiac muscle fibers were essential normal in the ADM+TPOL group and ADM+TPOH group with a little swelling of chondriosome and breakage and solution of actin filament. By immunohistochemistry stain method, we found IOD and 8-OHdG of ADM group was higher obviously than the other group and they were cut down in the group which TPO was used. However, there was no significant statistics difference between the ADM+TPOL group and ADM+TPOH group.Conclusions: TPO can protect the rats'heart by relieving adriamycin-induced cardiotoxicity . One of the protective mechanism is its anti-oxidative damage. |
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