睾酮对动脉粥样硬化内皮功能的影响  

Effect of testosterone on endothelial function in atherosclerosis

作　　者：高倩萍[1] 富路[1] 金红[2] 李元十[1] 李佳[1] 黄明学[1] 孟繁超[1] 

机构地区：[1]哈尔滨医科大学附属第一医院心血管内科三病房,黑龙江省哈尔滨市150001 [2]汕头大学医学院附属第一医院心内科,广东省汕头市515041

出　　处：《中国临床康复》2006年第25期96-98,共3页Chinese Journal of Clinical Rehabilitation

摘　　要：目的:探讨睾酮在雄兔动脉粥样硬化模型中是否具有保护内皮细胞功能的作用。方法:实验于2003-10/2004-06在哈尔滨医科大学第一临床医学院动物实验中心完成。选择雄性哈尔滨大耳白兔45只,随机分为5组,分别为安慰剂组、丙酸睾酮0.25,2.5,12.5mg/(kg·d)组及假手术组,每组9只。安慰剂组去势并给安慰剂;丙酸睾酮0.25,2.5,12.5mg/(kg·d)组家兔去势并分别予丙酸睾酮0.25mg/(kg·d),2.5mg/(kg·d),12.5mg/(kg·d)肌肉注射。3个月后,采集动物血样,检测血中睾酮水平、血脂浓度、纤溶酶原激活物抑制物活性,一氧化氮、内皮素、血管紧张素Ⅱ含量。麻醉后气栓法处死动物,分离主动脉,纵向剖开固定,计算斑块占总内膜面积的百分比。另外利用westernblot方法比较各组家兔雄激素受体表达量的变化。结果:进入结果分析安慰剂组、丙酸睾酮0.25,2.5,12.5mg/(kg·d)组及假手术组家兔数量分别为8,8,7,7及7只。①安慰剂组血清睾酮水平、一氧化氮含量显著低于其他组(P<0.05～0.01)。②安慰剂组纤溶酶原激活物抑制物活性、内皮素、血管紧张素Ⅱ含量及主动脉斑块面积百分比均显著高于其他组(P<0.05～0.01)。接近生理浓度犤0.25mg/(kg·d)犦的外源性睾酮可抑制兔纤溶酶原激活物抑制物活性,剂量增至10倍犤2.5mg/(kg·d)犦作用反而减弱,剂量再次增大至50倍犤1.25mg/(kg·d)犦又抑制纤溶酶原激活物抑制物活性犤(0.3344±0.0513,0.5051±0.0504,0.3742±0.1069)U/mL犦。③各组家兔的主动脉雄激素受体表达量差异无显著性意义(P>0.05)。结论:在高脂饮食诱发的兔动脉硬化模型中,睾酮可以保护内皮细胞功能,从而减轻动脉粥样硬化的程度。但外源性睾酮的作用并未随着剂量的增加而成倍增加,而且并未发现各组雄激素受体表达量有不同,考虑这种作用差别的原因位于受体后。AIM： To investigate the effect of testosterone on endothelial function in atherosclerosis of male rabbit models. METHODS： This experiment was conducted at the Animal Experimental Center, First Clinical Medical College, Harbin Medical University from October 2003 to June 2004. Totally 45 male Harbin rabbits were chosen and randomly divided into 5 groups： Group I： castrated rabbit treated with.placebo; Group 2： castrated rabbit treated with exogenous testosterone 0.25 mg/kg·d; Group 3： castrated rabbit treated with exogenous testosterone 2.5 mg/kg.d; Group 4： castrated rabbit treated with exogenous testosterone 12.5 mg/kg.d; Group 5： sham operation group, with 9 rabbits in each group. Three months later, the rabbits were sacrificed to collect blood sample. Then the following tests were performed：testosterone level, highdensity lipoprotein cholesterol （HDL-C）, low density lipoprotein cholesterol （LDL-C）, plasminogen activator inhibitor （PAI ） activity, nitric oxide （NO） content, endothelin （ET） and angio.tensin Ⅱ （Ag Ⅱ ） concentration. After anesthesia, the animals were euthanized with air embelus method. Aorta was isolated and then dissected longitudinally and fixed. The percent of atherosclerotic plague of aorta and total intima was calcu- lated. Change of androgen receptor was compared with Western blot in each group. RESULTS： 8, 8,7,7 and 7 rabbits respectively in Group 1, Group 2, Group 3, Group 4 and Group 5 entered the stage of result analysis. （1） Testosterone level and NO content were significantly decreased in the Group 1 than in the other groups （P 〈 0.05-0.01）. （2） PA I activity, ET, Ag Ⅱ content and the percent of atherosclerotic plaque of aortas were significantly higher in Group 1 than in other groups （P 〈 0.05-0.01）. Exogenous testosterone of 0.25 mg/（kg· d）which accesses to physiological concentration could inhibit PAI activity . The effect of dose at 10 times [2.5 mg/（kg·d）]was attenuated. When the dose increase to be

关 键 词：动脉粥样硬化 睾酮 内皮 血管 

分 类 号：R329.412[医药卫生—人体解剖和组织胚胎学]