睾酮对雄兔动脉粥样硬化斑块稳定性及血管活性物质的作用

Effects of Testosterone on Serum Vasoactive Substances and Atherosclerotic Plaque Stability in Rabbits

背景雄激素对动脉粥样硬化的作用尚存在争议,在斑块稳定性中的作用也不清楚。目的探讨睾酮对雄兔血管活性物质和动脉粥样硬化斑块稳定性的影响。方法将雄性新西兰纯种兔随机分为正常对照组(n=10)喂以普通饲料;假去势+球囊损伤颈动脉组(假去势组,n=15)、去势+球囊损伤颈动脉+生理盐水肌注组(去势组,n=23)、去势+球囊损伤颈动脉+生理剂量睾酮肌注组[补充睾酮组,6mg/(kg.2周),n=15]均喂以高脂饲料。在实验第8周随机处死部分动物,观察颈动脉病变的形态特征,抽血测睾酮、血管紧张素Ⅱ(AngⅡ)、肾上腺髓质素(ADM)、神经肽Y、降钙素基因相关肽(CGRP)水平。结果去势组兔血睾酮水平显著降低。补充睾酮可减少兔动脉粥样斑块的面积和内膜中层厚度(IMT)(斑块面积:假去势组(42.0±16.6)%比补充睾酮组(44.2±10.5)%比去势组(64.2±17.5)%,P<0.05;IMT:假去势组(759.3±92.4)比补充睾酮组(790.3±84.0)比去势组(941.9±119.2)μm,P分别<0.01、0.05],增加斑块纤维帽厚度和胶原含量[纤维帽厚度:假去势组(122.3±13.2)比补充睾酮组(122.6±17.3)比去势组(100.9±14.2)μm,P<0.05;胶原含量:假去势组(24.5±7.9)比补充睾酮组(23.2±7.2)比去势组(12.9±3.5),P<0.05]。补充睾酮可明显降低兔血AngⅡ和神经肽Y水平,增加ADM和CGRP的水平(P<0.05)。结论生理水平睾酮可以影响雄兔血浆血管活性物质水平,可抑制动脉粥样硬化斑块进展,增强斑块的稳定性。

Background The roles of androgen in atherosclerosis progress and plaque stability remain unclear. Objective To determine the effect of testosterone on serum vasoactive substances and atheroselerotic plaque stability in rabbits. Methods New Zealand white rabbits were underwent balloon induced carotid artery injury. Castrated rabbits were fed with high fatty diet, and randomized to following approaches： sham castrated operation（n= 15） or castrated operation without treatment（ n= 23）or testosterone treatment [6 mg/（kg · two weeks）, n=15] to maintain a physiological level of testosterone, rabbits fed with normal diet served as controls（n= 10）. Eight weeks after operation, pathological changes of the carotid artery were examined. Serum testosterone, angiotensin Ⅱ [Ang Ⅱ）, adrenomedullin [ ADM）, neuropeptide Y [ NPY） and calcitonin gene-related peptide[ CGRP） were determined. Results Testosterone treatment decreased the plaque area and the carotid intimal-media thickness（IMT） [ plaque area ： sham castrated operation group ： （ 42.0 ±16.6 ）%, testosterone group （ 44.2 ±0.5 ） % vs castrated operation group （64.2±17.5）%, both P〈0.05; IMT： sham castrated operation group （759.3±92.4）, testosterone group （790. 3±84.0） vs castrated operation group （941.9±119.2）μm, P〈0. 01, 0.05 respectively]. Testosterone treatment also increased the fibrous cap thickness and collagen content of the plague [fibrous cap thickness： sham castrated operation group （ 122.3 ± 13.2 ）, testosterone group （ 122.6 ± 17.3 ） vs castrated operation group （ 100.9±14.2 ）/lm, P〉0. 05 ; collagen content ： sham castrated operation group （ 24.5 ±7.9 ）, testosterone group （23.2±7.2） vs castrated operation group {12.9±3.5）, P〈0.05], with concomitantly decreased the levels of serum Ang Ⅱ and NPY, and increased the levels of ADM and CGRP. Conclusion Testosterone at physiological level might inhibited atherosclerotic plaque growth and increased stability in male rabbits which was associated with decreases in vasoactive substances （Ang Ⅱ, NPY and CGRP）.