磷酸肌酸对阿霉素引起的大鼠心脏毒性的预防保护作用

目的:探讨磷酸肌酸对大鼠阿霉素心脏毒性的保护作用及其作用机制。方法:将SD大鼠随机分为3组,每组10只。生理盐水对照组:每天腹腔注射与阿霉素等量的生理盐水;阿霉素组:实验中前3天每天腹腔注射生理盐水,第4天开始在腹腔注射生理盐水后30分钟给予阿霉素(3mg.kg-1),隔日1次,共给药7次;磷酸肌酸钠联合阿霉素组:实验中前3天每天腹腔注射磷酸肌酸钠(200mg.kg-1),第4天开始给予磷酸肌酸钠30分钟后腹腔注射阿霉素(3mg.kg-1),隔日1次,共给药7次。处死大鼠后作HE染色,光镜下观察各组大鼠心肌病理形态学变化,分别测定大鼠血清、心肌组织中丙二醛(MDA)含量、超氧化物岐化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)活性变化。结果:与生理盐水对照组大鼠比较,阿霉素组大鼠血清、心肌MDA含量都显著升高,而SOD、GSH-PX活性均降低(P<0.05)。给予磷酸肌酸钠治疗后明显降低了血清、心肌组织中MDA含量,增加了SOD、GSH-PX活性,与阿霉素组相比有统计学意义(P<0.01)。光镜下观察HE染色的阿霉素组心肌组织结构损伤明显,而磷酸肌酸钠联合阿霉素组心肌细胞结构破坏减轻。结论:磷酸肌酸对阿霉素引起的心肌损伤具有保护作用,其作用机制可能与磷酸肌酸能有效改善心肌能量代谢,减少氧自由基引起的心肌氧化性损害、保护抗氧化酶SOD、GSH-PX活性有关。

Protective effect of phosphocreatine on myocardium injury induced by adriamycin in rats

Objective:To observe the protective effect and mechanism of phosphocreatine(CP) injection on the myocardiam injury induced by adriamycin(ADM)in rats.Methods:SD rats were randomly divided into three groups.In the control group,normal saline was ip injected at a dose of adriamycin(ADM) every day.The ADM group was given ip injection of normal saline once a day for 3 days,and ADM at a dose of 3mg·kg-1 30 minutes after normal saline from the 4th day,once every other day for 7 times.The phosphocreatine(CP) Na and adriamycin(ADM)group was given ip injection of phosphocreatine(CP) Na at a dose of 200mg·kg-1 30 minutes after normal saline from the 4th day,once every other day for 7 times.The activities of SOD,GSH-PX and the level of malondialdehyde(MDA)in serum and myocardial were assayed at the same time,the rat myocardial pathomorphism was detected.Results: Compared with normal saline group,the serum and myocardial MDA content was higher,and the serum and myocardial SOD,GSH-PX activities were lower in adriamycin(ADM)group(P<0.05);Compared with adriamycin(ADM) group,the phosphocreatine(CP) Na and adriamycin(ADM)group could decrease MDA content and increase SOD,GSH-PX activities(P<0.01).The protection of myocardial pathological damage in therapy group was improved.Conclusion:Phosphocreatine(CP) has protective effect on the myocardium injury induced by adriamycin in rats,and the mechanism may related with that phosphocreatine can improve myocardial energy metabolize,decrease myocardium injury of free radicals and protect SOD,GSH-PX.