硫化氢供体对阿霉素心肌病大鼠氧化应激作用的影响  

Effect of hydrogen sulfide donor on oxidative stress of myocardium in adriamycin-induced dilated cardiomyopathy rats

作　　者：苏钰雯[1] 杜军保[1] 韩薇[1] 唐朝枢[2] 

机构地区：[1]北京大学第一医院儿科 [2]北京大学第一医院心血管病研究所,北京100034

出　　处：《中国病理生理杂志》2008年第8期1469-1474,共6页Chinese Journal of Pathophysiology

基　　金：国家杰出青年科学基金资助项目(No.30425010);国家重点基础研究发展规划项目(No.2006CB503807);国家自然科学基金资助项目(No.30630031)

摘　　要：目的:探讨外源性给予硫化氢供体硫氢化钠(NaHS)对阿霉素(adriamycin,ADR)心肌病大鼠氧化应激作用的影响。方法:雄性Wistar大鼠54只,随机分为5组:(1)ADR组(n=12):腹腔注射ADR,每次2.5mg/kg,每周1次,共用药10周;(2)ADR+小剂量NaHS组(n=12):ADR用药方法同ADR组,同时经腹腔注射NaHS,2.8μmol·kg-1·d-1,连续用药10周;(3)ADR+大剂量NaHS组(n=12):ADR用药方法同ADR组,同时经腹腔注射NaHS,14μmol·kg-1·d-1,连续用药10周;(4)对照组(n=9):用相同容量的生理盐水代替ADR,给药方法同ADR组;(5)NaHS组(n=9):经腹腔注射NaHS,14μmol·kg-1·d-1,连续用药10周。于第10周检测大鼠心功能和血流动力学指标,并测定其血清及心肌组织中H2S、脂质过氧化物丙二醛(MDA)的含量以及超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)的活性,比较其中的差异。结果:ADR组大鼠心功能较对照组明显降低(均P<0.01),且血清及心肌组织H2S含量均明显低于对照组(P<0.01),MDA含量明显较对照组升高(均P<0.01),SOD的活性明显降低(均P<0.01),GSH-Px的活性亦明显降低(血清及心肌组织:P<0.05,P<0.01);经外源性补充H2S供体NaHS后,大鼠心功能较前明显改善,ADR+大剂量NaHS组心肌组织中过氧化产物MDA含量明显降低(均P<0.01),而血清MDA含量无明显差异(P>0.05);ADR+大剂量NaHS组血清SOD活性明显升高(P<0.01),而心肌组织SOD活性无明显差异(P>0.05);ADR+大剂量NaHS组心肌组织GSH-Px活性明显增高(均P<0.05),而血清GSH-Px活性无明显差异(P>0.05)。结论:硫化氢参与了大鼠阿霉素心肌病的发病过程,外源性补充硫化氢供体NaHS可以改善阿霉素心肌病大鼠心功能,降低心肌组织中脂质过氧化物的含量,显著提高抗氧化酶体系的活性,减轻氧化应激损伤,从而参与对大鼠心肌的保护机制。AIM： To investigate the effect of hydrogen sulfide （ H2S） donor （NAHS） on oxidative stress of adriamycin - induced dilated cardiomyopathy rats. METHODS ： Weight - matched adult male Wistar rats were randomly divided into 5 groups as follows ： （ 1 ） ADR group （ n = 12）, in which 2. 5 mg/kg of adriamycin was injected intraperitoneally once a week for 10 weeks （total dose of 25 mg/kg）. （2） ADR ＋ small -dose NariS group （n = 12）, in which the dosage and the use of adriamycin were as mentioned above, while NariS solution was injected to rats at a dosage of 2. 8 μmol·kg^-1·d^-1 at the same time. （ 3 ） ADR ＋ large - dose NariS group （ n = 12 ）, in which the dosage and the use of adriamycin were as mentioned above, while NariS solution was injected to rats at a dosage of 14 μmol·kg^-1·d^-1 at the same time. （4） Control group （n = 9 ）, in which an equivalent volume of physiological saline was administered weekly for a total of 10 weeks. （5） NariS group （ n = 9 ）, in which 14 μmol/kg of NariS solution was injected to rats intraperitonealy once a week for 10 weeks. Hemodynamic and echocardiographic measurements were obtained 10 weeks after the treatment. Meanwhile, H2S and malondialdehyde （MDA） concentrations, the activities of superoxide dismutase （SOD） and glutathione peroxidase （GSH -Px） in serum and myocardial tissues were evaluated, respectively. RESULTS： The cardiac functions in the group of ADR rats depressed obviously. H2S concentrations, SOD and GSH- Px activities in serum and myocardial tissues of ADR group rats were all significantly decreased as compared with those in the control group （P 〈 0. 01 ）. The MDA concentrations in serum and myocardial tissues in ADR group rats were both increased significantly （ P 〈 0. 01 ）. Exogenous administration of H2S donor NariS markedly attenuated ADR- induced cardiac dysfunction, and MDA concentration in myocardial tissues was significantly reduced （P 〈 0. 01 ）. Serum SOD activ

关 键 词：硫化氢 阿霉素 心肌病 充血性 氧化性应激 

分 类 号：R725.4[医药卫生—儿科]