Intervension effects of doxazosin and its enantiomers on myocardial injury and cell cycle changes of rabbits fed with high fat diet / 解放军医学杂志

ABSTRACT

Objective To investigate the effects of (?)doxazosin [(?)DOX] and its enantiomers on the myocardial morphology,cell cycle and cell apoptosis in rabbits fed with high fat diet. Methods Male New Zealand white rabbits were fed with high fat diet for 4 weeks. Forty such rabbits with hyperlipemia were then divided into atherogenic diet group (model),model + (-)doxazosin [(-)DOX] group,model + (+)doxazosin [(+)DOX] group and model + (?)DOX group (10 each). Another 10 rabbits were included as normal control group. In those drug-treated groups,1.0mg/kg of doxazosin or its enantiomers were intraperitoneally administered for 9 weeks; rabbits in normal control group and atherogenic diet group were given sterile distilled water. Percentages of myocardial cells in G0/G1 phase and in S phase,proliferation index (PI) and apoptotic rate of myocardial cells were compared among the groups,and the effects of doxazosin and its enantiomers were evaluated. Results Of the animals in atherogenic diet group,the proportion of myocardial cells in G0/G1 phase increased significantly (P0.05). No histomorphological alterations were observed in myocardial cells of the rabbits in normal control group. Pathological changes in myocardial cells were observed in the rabbits of atherogenic diet group,such as vacuolar degeneration,fatty degeneration,focal myocardial necrosis,myocardial fibrosis and focal lymphocyte infiltration. The pathological changes in myocardial cells were significantly ameliorated in the animals in (-)DOX and (?)DOX group,but aggravated in the rabbits of (+)DOX group. Conclusions A long term treatment with (-)DOX in the rabbits may improve the histopathological changes in myocardial cells caused by high fat diet. (-)DOX and (+)DOX may have a optical selective effect.