睾酮及氟他胺对雄兔动脉粥样硬化斑块稳定性与血清炎症因子的调节

Regulation of Atherosclerotic Plaque Stability and Inflammatory Reaction by Testosterone and Flutamide in Male Rabbits

目的探讨睾酮和氟他胺对动脉粥样硬化斑块稳定性与血清炎症因子的调节作用。方法主动脉病理切片行HE染色和Masson氏三色染色。血浆睾酮采用Advia Centaur免疫检测系统测定,血清肿瘤坏死因子和白细胞介素6采用放射免疫测定,血清可溶性细胞间粘附分子1和基质金属蛋白酶2应用酶联免疫吸附测定法检测。结果雄兔去睾丸后血浆睾酮水平显著降低,补充十一酸睾酮(每2周6mg/kg)使血浆睾酮恢复到正常水平,而且十一酸睾酮这一作用不受雄激素受体拮抗剂氟他胺的影响。去睾丸雄兔补充十一酸睾酮显著减小动脉粥样斑块的面积和内膜厚度,并使斑块纤维帽增厚、胶原含量增加。然而,同时补充雄激素受体拮抗剂氟他胺使去睾丸雄兔动脉粥样斑块的面积和内膜厚度增加,并使斑块纤维帽厚度减低、胶原含量下降。与假手术高脂喂养雄兔比较,去睾丸雄兔血清肿瘤坏死因子、白细胞介素6、可溶性细胞间粘附分子1和基质金属蛋白酶2显著升高;去睾丸雄兔补充十一酸睾酮后,血清肿瘤坏死因子、白细胞介素6、可溶性细胞间粘附分子1和基质金属蛋白酶2较单纯去睾丸雄兔明显降低;去睾丸雄兔同时补充氟他胺与十一酸睾酮,血清肿瘤坏死因子、白细胞介素6、可溶性细胞间粘附分子1和基质金属蛋白酶2水平再次显著升高。结论睾酮与氟他胺可以调节雄兔动脉粥样硬化斑块进展与斑块的稳定性,并影响其血清炎症因子水平。

Aim To determine the influence of testosterone and flutamide on atheroselerofie plaque stability and inflammatory reaction. Methods Pathological sections of aorta were performed with hematoxylin-eosin staining and Masson＇s trichrome staining. Total plasma testosterone was measured using Advia Centaur immunoassay system. The contents of serum tu- mor neeresis factor-α （TNF-α） and intedeukin-6 （IL-6） were assayed using radio-immunoassay kit. The concentrations of serum soluble intercellular adhesion molecule-1 （sICAM-1） and matrix metallopeptidase-2 （MMP-2） were assayed using enzyme linked immunosorbent assay （ELISA） kit according to the procedure described by the manufacturer. Results Testosterone undecanoate replacement reduced the plaque area and the aortic intimal thickness, and increased the fibrous cap thickness and collagen contents in castrated rabbits. However, presence of flutamide increased the plaque area and the aortic intimal thickness, and decreased the fibrous cap thickness and collagen contents in castrated rabbits gain. Levels of serum TNF-α, IL-6, sICAM and MMP-2 increased in cholesterol-rich diet rabbits compared with standard diet rabbits. Castration caused an increase in levels of serum TNF-α, IL-6, sICAM and MMP-2 in castrated rabbits compared with sham-operated rabbits. Treatment of testosterone undecanoate reduced the levels of serum TNF-α, IL-6, sICAM and MMP-2 in castrated rabbits. However, presence of flutamide increased the levels of serum TNF-α, IL-6, sICAM and MMP-2 again. Conclusion Testosterone at physiological dose and flutamide can influence atheroselerotic plaque growth and stability and the levels of inflammatory factors.