摘要
目的探讨给予外源性硫化氢(H2S)供体硫氢化钠(NaHS)对阿霉素(ADR)心肌病大鼠心功能及心肌结构的影响及其作用机制。方法雄性Wistar大鼠54只,随机分5组(1)ADR组;(2)ADR+小剂量NaHS组;(3)ADR+大剂量NaHS组;(4)对照组;(5)NaHS组。药物均腹腔注射,连续用药10周,检测心功能和血流动力学指标,于光镜及电镜下观察显微及超微结构,并测定其血浆及心肌组织中H2S含量。结果阿霉素组大鼠心功能较对照组明显降低(P<0.01),心肌组织呈心肌病样改变,且血浆及心肌组织中H2S含量均明显低于对照组(P<0.001)。经补充外源性H2S供体NaHS后,大鼠心功能较前明显改善,心肌组织病理损害程度明显减轻。结论H2S参与了大鼠阿霉素心肌病的发病过程,补充外源性H2S可以改善阿霉素心肌病大鼠心功能,减轻心肌损伤。
Objective This study was designed to investigate the importance of H2S in rats with adriamycin-induced dilated cardiomyopathy. Methods Weight-matched adult male Wistar rats were randomly divided into 5 groups as follows ： （ 1 ） the ADR group （ n = 12 ） where adriamycin （2.5 mg/kg） was given once a week ; （2） ADR ＋ smalldose NariS group （ n = 12） where NariS solution [ 2.8 μmol/（ kg · d） ] was given ; （3） ADR ＋ large-dose NariS group （ n = 12 ） where NariS solution [ 14 μmol/（ kg · d ） ] was given ; （4） the control group （ n = 9 ） where physiological saline was administered instead of adriamycin. （ 5 ） NariS group （ n = 9 ） where NariS solution [ 14 μmol/（ kg · d）]was given. Hemodynamic and echocardiographic measurements were carried out after treatment. Histological examination was implemented at the 10th week after the rats were sacrificed. Meanwhile, H2S concentrations in serum and myocardial tissues were evaluated by modified sulfide electrode method. Results The heart function of ADR rats decreased obviously. Pathological examination demonstrated that characteristics consistent with cardiomyopathy were found in ADR group. H2S concentrations in serum and myocardial tissues of the rats in ADR group were both significantly decreased as compared with those in the control group （both P 〈0. 001 ）. Exogenous administration of the H2S donor Naris improved the heart function. Histological sections showed that myocyte necrosis and myocardial injury were lessened. Conclusion H2S may play an important role in the development of adriamycin-induced dilated cardiomyopathy. Administration of exogenous H2S could protect myocardial structure and contractile activity.
出处
《基础医学与临床》
CSCD
北大核心
2007年第11期1193-1197,共5页
Basic and Clinical Medicine
基金
国家自然科学基金(30630031)
国家重点基础研究发展规划(2006CB503807)
国家杰出青年科学基金(30425010)
关键词
硫化氢
阿霉素心肌病
心肌组织超微结构
hydrogen sulfide
adriamycin-induced dilated cardiomyopathy
ultra-micro-structure of myocardial tissues
