多沙唑嗪及其光学异构体对高脂饮食诱导兔心肌组织损伤和细胞周期改变的干预效果  

Intervension effects of doxazosin and its enantiomers on myocardial injury and cell cycle changes of rabbits fed with high fat diet

作　　者：曹雪滨[1] 王荣英[2] 杨梅[1] 张刚[1] 崔英凯[1] 任雷鸣[3] 

机构地区：[1]河北保定解放军252医院心内科,071000 [2]石家庄河北医科大学第二附属医院急诊科,050000 [3]石家庄河北医科大学药学院药理学研究室,050017

出　　处：《解放军医学杂志》2010年第6期706-709,共4页Medical Journal of Chinese People's Liberation Army

基　　金：国家自然科学基金(30940088);河北省自然科学基金(C2009001070)

摘　　要：目的探讨消旋多沙唑嗪[(±)DOX]及其光学异构体对高脂饮食家兔心肌组织形态学、心肌细胞的增殖周期以及细胞凋亡的影响。方法兔高脂饮食4周后,选取造模成功的家兔随机分为4组(n=10):高脂模型组、左旋多沙唑嗪[(-)DOX]组、右旋多沙唑嗪[(+)DOX]组和消旋多沙唑嗪[(±)DOX]组。另设普通饮食组(n=10)。(-)DOX组、(+)DOX组和(±)DOX组均连续9周腹腔注射相应药物1.0mg/kg,普通饮食组和高脂模型组给予无菌双蒸水腹腔注射。比较各组心肌细胞凋亡率、G0/G1期细胞百分率、S期细胞百分率和细胞增殖指数(PI),并分析各组心室肌病理变化。结果与普通饮食比较,高脂模型组心肌组织的G0/G1期细胞显著增多(P<0.05),而S期细胞比例和细胞增殖指数(PI)显著降低(P<0.05);(-)DOX及(±)DOX组的G0/G1期细胞百分率、S期细胞百分率和细胞PI均恢复至普通饮食组水平。各组的心肌细胞凋亡率无显著差异(P>0.05)。普通饮食组心肌组织未见异常;高脂模型组可见心肌细胞出现不同程度的病理学改变;(-)DOX组及(±)DOX组高脂饮食诱发的家兔心室肌病理变化显著减轻,而(+)DOX组心室肌病理变化加重。结论长时间给予(-)DOX可改善高脂饮食所致的家兔心脏损害。对于高脂血症相关的心室肌病理学改变和细胞增殖周期变化,(-)DOX和(+)DOX的作用具有显著的光学选择性。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）,while the cells in S phase and PI value decreased significantly （P0.05）. Of the animals in （-）DOX group and （±）DOX group,proportions of myocardial cells in G0/G1 phase and S phase,and PI values returned to the levels similar to that in normal control group. No significant changes were found in the apoptotic rate of myocardial cells among the rabbits in all the groups （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. C

关 键 词：多沙唑嗪 心肌 细胞增殖 细胞凋亡 脂类 

分 类 号：R589.21[医药卫生—内分泌]