Effects of Fasudil at Different Doses on Cardiomyocyte Apoptosis and Protein Expression Levels of bcl-2,c-myc in the Rats with Pressure Overloaded Heart Failure
  Revised:January 22, 2007
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KeyWord:Heart failure,Apoptosis,cardiomyocytes,Fasudil,Dosage
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      Objective To study the mechanisms of action of fasudil at different doses on the cardiomyocyte apoptosis in the rats with pressure overloaded heart failure following coarctation of the ascending aorta.Methods A rat model of heart failure was created by coarctation of ascending aorta.40 female Wistar rats with heart failure were divided randomly into four groups,including natrium chloride (0.1 mL),fasudil(1 mg/kg),fasudil(5 mg/kg),fasudil(20 mg/kg)(n=10 per group),which were treated by i.p injection b.i.d for 4 weeks.Another 10 age-matched sham-operated rats were used as control.The rats were observed for another 20 weeks after coarctation of the ascending aorta operation.Hemodynamic parameters,ratio of LV weight to body weight,cardiomyocyte apoptosis,protein expression levels of bcl-2 and c-myc were investigated in all the groups.Results Fasudil intervention reduced cardiomyocyte apoptosis,decreased protein expression level of c-myc and improved protein expression level of bcl-2 in rats with chronic cardiac dysfunction,in a dose-dependent manner.The number of cardiomyocyte apoptosis and the protein expression level of cmyc were significantly lower and the level of bcl-2 was markedly higher in the group of high dose fasudil than those in the groups of low dose fasudil.Conclusions Fasudil can effectively decrease cardiomyocyte apoptosis,reduce the protein level of c-myc and increase bcl-2 protein level dose-dependently,which may be one of mechanisms of prevention and treatment of heart failure.
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