The role of hydrogen sulfide in adriamycin-induced dilated cardiomyopathy in rats / 中国药理学通报

ABSTRACT

Aim To investigate the effect of hydrogen sulfide(H2S) on apoptosis of myocardial tissues of adriamycin-induced dilated cardiomyopathy in rats and to explore the underlying mechanisms.Methods Weight-matched male Wistar rats were randomly divided into 5 groups as follows(1) ADR group(n=12),2.5 mg?kg-1 of adriamycin was injected intraperitoneally once a week for 10 weeks(total dose of 25 mg?kg-1);(2) ADR+small-dose-NaHS group(n=12),the dosage and use of adriamycin were as mentioned above,while NaHS solution was injected to rats at a dosage of 2.8 ?mol?kg-1?d-1 at the same time;(3) ADR+large-dose-NaHS group(n=12),the dosage and use of adriamycin were as mentioned above,while NaHS solution was injected to rats at a dosage of 14 ?mol?kg-1?d-1 at the same time;(4) ADR+PPG group(n=12),in which the dosage and use of adriamycin were as mentioned above,while PPG solution was injected to rats at a dosage of 30 mg?kg-1?d-1;(5) control group(n=9),an equivalent volume of physiological saline was administered weekly for 10 weeks.(6) NaHS group(n= 9),14 ?mol?kg-1 of NaHS solution was injected to rats intraperitoneally for 10 weeks.Hemodynamic and echocardiographic measurements were obtained 10 weeks after treatment.Histological examination was implemented at the 10th week after sacrificed.And apoptotic index,Fas and Bcl-2 expressions in myocardiocytes were analyzed semiquantitatively by TUNEL or immunohistochemical analysis.Meanwhile,H2S concentrations in serum and myocardial tissues were evaluated by a modified sulfide electrode-based method.Results Left ventricular systolic pressure(LVSP),difference of left ventricular pressure(△LVP=left ventricular systolic pressure minus left ventricular diastolic pressure) and ventricular peak rate of contraction(+LV dp/dtmax),peak rate of relaxation(-LV dp/dtmax) were significantly reduced in the group of ADR rats(P0.05).Conclusion H2S might play an important role in the development of adriamycin-induced dilated cardiomyopathy.Administration of exogenous H2S could protect the cardiac function and myocardial pathological lesions via the down-regulation of augmented myocardiocyte apoptosis.