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Effect of hydrogen sulfide donor on oxidative stress of myocardium in adriamycin-induced dilated cardiomyopathy rats
Authors:SU Yu-wen  DU Jun-bao  HAN Wei  TANG Chao-shu
Institution:1.Department of Pediatrics, 2Key Laboratory of Molecular Cardiovascular Medicine, Ministry of Education, 3Institute of Cardiovascular Research, Peking University First Hospital, Beijing 100034, China. E-mail:junbaodu1@126.com
Abstract:AIM: To investigate the effect of hydrogen sulfide (H2S) 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 NaHS group (n=12), in which the dosage and the use of adriamycin were as mentioned above, while NaHS solution was injected to rats at a dosage of 2.8 μmol·kg-1·d-1 at the same time. (3) ADR + large-dose NaHS group (n=12), in which the dosage and the use of adriamycin were as mentioned above, while NaHS 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) NaHS group (n=9), in which 14 μmol/kg of NaHS solution was injected to rats intraperitonealy once a week for 10 weeks. Hemodynamic and echocardiographic measurements were obtained 10 weeks after the treatment. Meanwhile, H2S 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. H2S 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 H2S donor NaHS markedly attenuated ADR-induced cardiac dysfunction, and MDA concentration in myocardial tissues was significantly reduced (P<0.01). Serum SOD activity was obviously increased in ADR+large-dose NaHS group compared with control group (P<0.01), and GSH-Px activity in myocardial tissues was markedly increased in ADR+large-dose NaHS group compared with control group (P<0.05). CONCLUSION: H2S might play an important role in the development of adriamycin-induced dilated cardiomyopathy. Administration of exogenous H2S effectively improves myocardial contractile activity, reduces the accumulation of lipid peroxides and increases the capability of antioxidants to inhibit oxidative stress and prevents myocardial damage.
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