Objective To study the effect of doxazosin (DOX) on serum lipid levels and aortic artery pathological morphology in atherosclerotic rabbit models.Methods New Zealand male rabbits were randomly divided into three groups:normal diet group, atherogenic diet group, DOX-treated group, each group consisting of ten rabbits.Normal diet group was fed with normal feed stuff,the latter two groups were fed with high cholesterol feed stuff.After four weeks,intraperitoneal injected with DOX 1 rog/kg once daily on the basis of atherogenic diet, then, the rabbits of DOX-treated group were treated for nine weeks.Blood samples were drawn from the rabbits before the experiment and at the end of the fourth, the seventh, the tenth, the thirteenth week of the experiment respectively.The blood samples were analyzed for TG,TC and LDL-C.Thoracic aortas were excised and processed for pathological morphology studies.Results There were no interaction between the time points and groups in the serum concentration of TC,TG and LDL-C ( P ＞0.05).In atherogenic diet group, the serum concentration of TC at the end of the fourth, the seventh, the tenth, and the thirteenth week were (28.63±7.65) mmol/L, (35.26±7.88) mmol/L, (41.16±4.11) mmol/L,and (40.83± 3.90) mmol/L,the serum concentration of LDL-C at the end of the fourth the seventh, the tenth,and the thirteenth week were (16.21±9.59) mmol/L,(24.64±8.55) mmol/L,(25.39±4.19) mmol/L,and (28.46±3.81) mmol/L, TC and LDL-C significantly increased in the atherogenic diet groups ( P ＜0.01).But in DOX-treated diet group, the serum concentration of TC at the end of the fourth, the seventh, the tenth, and the thirteenth week were (29.36 ± 7.94) mmol/L, (35.58±11.58) retool/L, (38.41 ±6.84) mmol/L,and (37.59±6.09) mmol/L,the serum concentration of LDL-C at the end of the fourth,the seventh,the tenth,and the thirteenth week were (17.66±8.84) mmol/L, (18.45± 8.21) mmol/L, ( 26.93 ± 6.38) mmol/L, and ( 25.50 ± 6.70) mmol/L, no significant changes were found in DOXtreated diet group( P ＞0.05).In DOX-treated group, the percentage of plaque covered area to total area (30.40 ± 9.04) ％ was significantly reduced comparing with that of atherogenic diet group(75.40± 17.21) ％ ( P ＜0.01).HE pathology staining of thoracic aortas:in DOX-treated group, the degree of atherosclerotic changes was lessened than that in atherogenic diet group.Conclusion DOX can suppress the development of atherosclerosis by pathological morphology, and improve LDL-C and TC disorder mildly in the rabbits fed by an atherogenic diet.The improvements in TC and LDL-C induced by DOX, however, might not be the reason for exploration about anti-atherosclerosis in the rabbits fed by an atherogenic diet..%目的 观察多沙唑嗪(DOX)对动脉粥样硬化兔模型血脂水平及主动脉病变的影响.方法 健康雄性新西兰兔随机分为普通饮食组、高脂饮食组、DOX治疗组,每组10只.普通饮食组予普通饲料喂养,其余两组给予高脂饲料.喂养4周后,DOX治疗组每日定时给予DOX 1 ml/kg腹腔注射,连续给药9周.分别于实验开始时(0周、4周末、7周末、10周末、13周末)抽取空腹血标本,检测各组血清总胆固醇(TC)和甘油三酯(TG)和低密度脂蛋白胆固醇(LDL-C).实验结束时(第13周末)处死动物,取胸主动脉做病理形态学观察.结果 3组血清TC、TG、LDL-C水平组间与不同时点交互作用差异无统计学意义(P>0.05).高脂饮食组兔血清TC第4周末(28.63±7.65)mmol/L,第7周末(35.26±7.88)mmol/L,第10周末(41.16±4.11)mmol/L,第13周末(40.83±3.90)mmol/L,血清LDL-C第4周末(16.21±9.59)mmol/L,第7周末(24.64±8.55)mmol/L,第10周末(25.39±4.19)mmol/L,第13周末(28.46±3.81)mmol/L,随高脂饲养的时间延长(第10～13周),血清TC、LDL-C水平进一步显著升高(P0.05).DOX治疗组胸主动脉内膜斑块覆盖面积占总面积的百分比(30.40±9.04)%较高脂饮食组(75.40±17.21)%差异有统计学意义(P<0.01);苏木精-伊红染色结果显示:DOX治疗组兔胸主动脉动脉粥样硬化病变程度明显低于高脂饮食组.结论 病理学证实DOX有明确的抗动脉粥样硬化作用,并对高血脂兔的血清TC,LDL-C紊乱具有轻度的改善作用,该作用可能不是其抗动脉粥样硬化的主要作用机制.
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