促红细胞生成素对阿霉素致大鼠膈肌损伤的保护作用
The protective effect of erythropoietin on diaphragm injury induced by doxorubicin in rats
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摘要: 目的：探讨促红细胞生成素(erythropoietin，EPO)对阿霉素致大鼠膈肌损伤的保护作用。方法：雄性SD大鼠30只，随机均分为对照组、模型组、EPO组。应用离体灌流大鼠膈肌肌条方法，分别测量单收缩张力(Pt)、最大强直张力(Po)、峰值收缩时间(CT)、半舒张时间(1/2RT)、张力最大上升速率(+dT/dtmax)、张力最大下降速率(-dT/dtmax)、张力-频率曲线变化，同时测定膈肌组织超氧化物歧化酶(SOD)活力和丙二醛(MDA)的含量。电镜观察膈肌细胞超微结构变化。结果：模型组大鼠膈肌Pt、Po、+dT/dtmax、-dT/dtmax均明显低于对照组(P；0.01)，EPO组大鼠膈肌的Pt、Po、+dT/dtmax、-dT/dtmax与对照组差异均无统计学意义(P；0.05)。模型组的CT、1/2RT均明显长于对照组及EPO组(P；0.01)。予10、20、40、60、100 Hz频率的方波电压刺激膈肌时，模型组大鼠膈肌张力均明显低于对照组和EPO组(P；0.01)。与对照组比较，模型组大鼠膈肌组织的SOD活力明显降低，MDA含量明显升高(P；0.01)，EPO组的SOD活力提高，MDA含量与对照组比较差异无统计学意义(P；0.05)。电镜显示阿霉素导致膈肌细胞肌纤维肿胀，线粒体空泡化，EPO改善阿霉素造成的损伤。结论：阿霉素导致大鼠膈肌氧自由基生成增多，清除减少，收缩功能减低；EPO对阿霉素所致的膈肌损伤有保护作用。Abstract: 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.
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Key words:
- doxorubicin /
- erythropoietin /
- diaphragm /
- contraction /
- free radicals
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