多沙唑嗪光学异构体对高血脂家兔血脂水平的影响

目的:观察左旋多沙唑嗪(-)DOX、右旋多沙唑嗪(+)DOX和消旋多沙唑嗪(±)DOX对高血脂家兔血脂水平及动物死亡率的影响。方法:取普通级雄性新西兰大耳白兔,给予高脂饮食4周后,血清TC小于10mmol/L的8只家兔为普通饮食组,饲以标准饲料。血清TC大于10mmol/L的40只家兔随机分为4组(n=10):高脂模型组、高脂模型+(-)DOX组、高脂模型+(+)DOX组以及高脂模型+(±)DOX组。普通饮食组和高脂模型组家兔腹腔注射无菌双蒸水;其他3组家兔分别腹腔注射(-)DOX、(+)DOX和(±)DOX,连续9周。分析药物对兔血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)的影响。结果:饲以高脂饮食13周时模型组家兔死亡率达40%,远远高于普通饮食组家兔(10%),亦明显高于(±)DOX和(-)DOX处理组。模型组家兔随高脂饲养的时间延长,血清LDL-C水平进一步显著升高(P0.05和P0.01);而各药物处理组动物的血清LDL-C水平未显著升高(P0.05)。结论:(-)DOX和(±)DOX可提高高脂饮食家兔的生存率,并对高血脂家兔的血清LDL-C紊乱具有轻度的改善作用;该作用可能不是其提高高脂饮食家兔生存率的主要作用机制。

Effects of doxazosin and its enantiomers on serum lipid levels in rabbits fed by an atherogenic diet

Objective：To observe the effects of （-）doxazosin（DOX）,（＋）DOX and （±）DOX on serum lipid levels and the mortality rates of the rabbits fed by an atherogenic diet.Methods：Male white New Zealand rabbits were fed by an atherogenic diet for 4 weeks.8 rabbits whose serum TC 10 mmol/L were confirmed as normal diet group and were fed normally.40 rabbits whose serum TC 10 mmol/L were randomly divided into 4 groups （n=10）：atherogenic diet group,atherogenic diet with （-）DOX group,atherogenic diet with （＋）DOX group and atherogenic diet with （±）DOX group,which were intraperitoneally injected with （-）DOX,（＋）DOX and （±）DOX for 9 weeks respectively.Normal and atherogenic diet group were intraperitoneally injected with double distilled water.After 9 weeks administration of （±）doxazosin and its enantiomers,effects of the three agents on serum levels of total cholesterol（TC）,triglyceride（TG）,high density lipoprotein cholesterol （HDL-C） and low density lipoprotein cholesterol （LDL-C） were observed.Results：The mortality rate of the rabbits fed by an atherogenic diet for 13 weeks was 40%,and it was much higher than that of the rabbits fed by a normal diet （10%）.The mortality rates in the rabbits treated with （-）DOX and （±）DOX were lower than that in the rabbits fed by a normal diet （10%）.Serum LDL-C level of the rabbits was increased markedly after 4 weeks of atherogenic diet,and it was further increased significantly （P0.05 and P0.01） during the continued 9 weeks of atherogenic diet.However,serum LDL-C levels were not further increased significantly （P0.05） during the continued 9 weeks of atherogenic diet in the rabbits treated with （-）DOX,（＋）DOX and （±）DOX,respectively.Conclusion：（-）DOX and （±）DOX increase the survival rate and improve LDL-C disorder mildly in the rabbits fed by an atherogenic diet.The improvements in LDL-C induced by （-）DOX and （±）DOX,however,might not be the reason for exploration about the increased survival rate in the rabbits fed by an atherogenic diet.