睾酮对雄兔动脉粥样硬化斑块稳定性的影响及其机制研究

Effects of testosterone on atherosclerotic plaque stability and its mechanisms in male rabbits

目的探讨睾酮对雄兔血丙二醛、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)、血管紧张素Ⅱ(AngⅡ)、降钙素基因相关肽(CGRP)和动脉粥样硬化斑块稳定性的影响。方法 66只新西兰兔随机分为对照组(A组,10只);假去势+球囊损伤颈动脉组(B组,16只)、去势+球囊损伤颈动脉+生理剂量十一酸睾酮肌肉注射组(C组,16只)和去势+球囊损伤颈动脉+生理盐水肌肉注射组(D组,24只)。第8周观察兔颈动脉病变的形态特征,检测睾酮、丙二醛、SOD、GSH-PX、AngⅡ和CGRP水平。结果与D组比较,A组、B组、C组兔睾酮、SOD、GSH-PX和CGRP水平显著升高,丙二醛和AngⅡ水平显著降低(P<0.05,P<0.01);与A组比较,B组和C组兔丙二醛水平显著升高,SOD和GSH-PX水平显著降低;与D组比较,B组和C组兔校正斑块面积和颈动脉内膜中层厚度显著减小,纤维帽增厚、校正胶原面积明显增加(P<0.05,P<0.01)。结论生理剂量睾酮可以影响雄兔血丙二醛、SOD、GSH-PX、AngⅡ和CGRP水平,并可能影响动脉粥样硬化斑块进展与斑块的稳定性。

Objective To determine the influence of testosterone on serum concentrations of MDA, SOD,GSH-PX,Ang Ⅱ ,CGRP,and atherosclerotic plaque stability in male rabbits. Methods Sixty-six New Zealand white rabbits were randomly divided into 4 groups： group A（control group, n= 10）, group B（rabbits underwent balloon-induced carotid wall injury and sham castration operation, n = 16）,group C（rahbits underwent balloon-induced carotid wall injury plus castration operation and then treated with testosterone, n = 16） and group D（rabbits underwent balloon-induced carotid wall injury plus castration operation and then treated with placebo, n = 24）. The rabbits were fed with high fatty forage. After 8 weeks,some rabbits were sacrificed, the pathological changes of the carotid arteries were observed. Fasting blood samples were collected for examination of serum testosterone,MDA,SOD,GSH-PX,AngⅡ and CGRP. Results Testosterone level of group D was lower than that of the other groups. The levels of MDA, Ang Ⅱ were lower in group B and group C than in group D,the levels of SOD,GSH-PX,CGRP were higher in group B and group C than in group D. Pathologic examination revealed that the plaque area and the carotid IMT were significantly smaller in group B and group C than in group D,whereas the fibrous cap thickness and collagen content were significantly higher in group B and group C than in group D. Conclusions Testosterone at physiological dose can influence the levels of MDA,SOD,GSH-PX, Ang Ⅱ,CGRP and atherosclerotic plaque growth and stability in male rabbits.