The protective effect of erythropoietin on diaphragm injury induced by doxorubicin in rats

Objective:To explore the mechanism of protective effect of erythropoietin on the doxorubicin induced diaphragm injury in rats. Methods:Thirty rats were divided into three groups: normal control group(n=10),model group(n=10) and erythropoietin group(n=10).Diaphragm strips was isolated to observe peak twitch tension(Pt),maximum titanic tension(Po),time to peak contraction(CT),half relaxation time(1/2RT),maximal rates of contraction(+dT/dtmax),maximal rates of relaxation(-dT/dtmax) and force-frequency curve.Meanwhile,the activity of superoxide dismutase(SOD) and content of malondialdehyde(MDA) in diaphragm were also measured.Electron microscope was used to observe the changes of diaphragm cell ultrastructure. Results:Pt,Po,+dT/dtmax,-dT/dtmax in model group were lower than those in control group(P0.01),the above four indexes in erythropoietin group did not differ from those in control group.CT,1/2RT in model group were prolonged compared with that in control group and erythropoietin group(P0.01).Stimulated by the frequency of 10,20,40,60,100 Hz,diaphragm tension in model group was obviously decreased compared with that in control group and erythropoietin group(P0.01).SOD activity was decreased and MDA content was increased in model group compared with control group(P0.01),the difference of MDA was insignificant between control group and erythropoietin group(P0.05).Electron microscopy showed myofibrils were swollen and mitochondria were vacuolization in model group,erythropoietin can ameliorate the injury. Conclusions:Doxorubicin can depress the contraction of diaphragm and increase the production of oxygen free radicals and reduce their clearance;erythropoietin can protect diaphragm from damage by counteracting the above effects of doxorubicin.