标题：磷酸肌酸钠对阿霉素所致大鼠心肌损伤的保护作用及其机制研究

      作者：薛梅苓 1，杜小波 2    (1.兵器工业五二一医院药剂科，陕西 西安 710065；2.西安市华山中心医院药剂科，陕西 西安 710043)

      卷次： 2017年28卷7期

      【摘要】 目的 观察磷酸肌酸钠(SP)对阿霉素(ADM)所致大鼠心肌损伤的保护作用，并探讨其可能的作用机制。方法 应用随机数字表法将30只雄性SD大鼠分为空白对照组(n=10)、阿霉素组(ADR组，n=10)和磷酸肌酸钠组(SP组，n=10)。对照组腹腔注射生理盐水每日一次，ADR组隔日一次腹腔注射阿霉素建立阿霉素心肌损伤模型，SP组隔日一次腹腔注射磷酸肌酸钠(200 mg/kg)，30 min后注射阿霉素。实验结束后应用羟胺法测定各组大鼠超氧化物歧化酶(SOD)，应用硫代巴比妥法测定各组大鼠丙二醛(MDA)，应用ELISA法测定各组心肌酶谱[乳酸脱氢酶(LDH)、心肌天冬氨酸转氨酶(AST)、磷酸肌酸激酶(CK)、肌酸激酶同功酶(CK-MB) ]水平。结果 ADR组和SP组大鼠血清SOD水平分别为(47.11±9.64) μg/L、(80.9±17.98) μg/L，显著低于空白对照组的(89.12±18.23) μg/L，而MDA水平分别为(7.12±1.46) μg/L、(2.3±0.47) μg/L，显著高于空白对照组的(1.66±0.34) μg/L。SP组大鼠血清SOD水平高于ADR组，MDA水平低于ADR组，差异均有统计学意义(P<0.05)。ADR组和SP组大鼠血清心肌酶谱(LDH、AST、CK、CK-MB)水平分别为(1 307.79±267.50) U/L、(476.19±97.40) U/L、(961.29±196.63) U/L、(1 353.33±276.82) U/L和(713.79±146.02) U/L、(164.32±33.61) U/L、(387.09±79.18) U/L、(565.29±115.63) U/L，均明显高于空白对照组的(691.02±141.35) U/L、(130.68±26.73) U/L、(327.69±67.03) U/L、(487.08±99.63) U/L，而SP组大鼠的上述血清心肌酶谱水平均高于ADR组，差异均有统计学意义(P<0.05)。结论 磷酸肌酸钠干预可以减轻大鼠阿霉素心肌损伤，其保护作用的实现，可能是由于清除了氧自由基，增强了SOD的活性，减轻脂质过氧化反应，并修复了心肌细胞损伤。
      【关键词】 SD大鼠；磷酸肌酸钠；阿霉素；心肌损伤；氧自由基
      【中图分类号】 R-332 【文献标识码】 A 【文章编号】 1003—6350（2017）07—1033—03

Experimental study of sodium phosphocreatine to protect against adriamycin-induced cardiotoxicity injury inrats and its mechanism.
XUE Mei-ling 1, DU Xiao-bo 2. 1. Department of Pharmacy, the 521 Hospital of Weapon Industry,Xi'an 710065, Shaanxi, CHINA; 2. Department of Pharmacy, Xi'an Huashan Central Hospital, Xi'an 710043, Shaanxi,CHINA
【Abstract】 Objective To investigate the effect and possible mechanisms of sodium phosphocreatine (SP) toprotect against adriamycin-induced cardiotoxicity injury in rats. Methods Thirty cases of male SD rats were randomlydivided into blank control group (n=10, intraperitoneal injection of saline once a day), adriamycin group (n=10, intraperi-toneal injection of doxorubicin every other day to establish adriamycin myocardial injury model) and SP group (n=10, in-traperitoneal injection of SP every other day 200 mg/kg 30 min after the injection of doxorubicin). At the end of the ex-periment, the levels of superoxide dismutase (SOD) in each group were measured by hydroxylamine method. Malondial-dehyde (MDA) was determined by thiobarbital method. The myocardial enzymes such as lactate dehydrogenase (LDH),asparate aminotransferase (AST), creatine kinase (CK), creatine kinase-MB isoenzyme (CK-MB) levels were measured.Results The levels of serum SOD in ADR group and SP group were (47.11±9.64) μg/L, (80.9±17.98) μg/L, significant-ly lower than (89.12±18.23) μg/L in control group (P<0.05). The levels of serum MDA in ADR group and SP group were(7.12±1.46) μg/L, (2.3±0.47) μg/L, significantly higher than (1.66±0.34) μg/L in control group (P<0.05). The level of se-rum SOD in SP group was higher than that in ADR group, and the level of MDA in SP group was significantly lowerthan that in ADR group (P<0.05). The levels of serum myocardial enzymes (LDH, AST, CK, CK-MB) were (1 307.79±267.50), (476.19±97.40), (961.29±196.63) and (1 353.33±276.82) in ADR group and (713.79±146.02), (164.32±33.61),(387.09±79.18), (565.29±115.63) in SP group, which were significantly higher than (691.02±141.35), (130.68±26.73),(327.69±67.03), (487.08±99.63) in the control group (P<0.05). The levels of serum myocardial enzymes (LDH, AST,CK, CK-MB) in SP group were significantly higher than those in ADR group (P<0.05). Conclusion SP has protectiveeffect on adriamycin-induced cardiotoxicity injury, maybe through scavenging oxygen free radicals, enhancing the SODactivity, reducing lipid peroxidation and repairing myocardial cell damage.
      【Key words】 SD rats; Sodium phosphocreatine; Adriamycin; Myocardial injury; Oxygen free radicals·论 著·doi:10.3969/j.issn.1003-6350.2017.07.001