睾酮对人血管内皮细胞纤溶活性影响及机制

目的：观察睾酮对人血管内皮细胞分泌纤溶酶原激活物（tPA）、纤溶酶原激活物抑制物1（PAI-1）的影响及其机制。方法： 将体外培养的人血管内皮细胞（HUVEC）分为5个浓度睾酮组及单纯培养基对照组，MTT实验观察睾酮对细胞生长及活性影响。ELISA 法测各组tPA、 PAI-1含量。用雄激素受体拮抗剂(flutamide)预处理细胞后重复实验。结果： 生理及略低于生理剂量睾酮（3×10-10 mol/L-3×10-8 mol/L）可明显促进tPA 分泌（P＜0.01）；而大剂量则使tPA 含量明显减少（P＜0.01）。各睾酮组PAI-1含量均明显低于对照组（P＜0.05）。Flutamide 能有效消除睾酮的上述作用。结论： 生理浓度睾酮通过雄激素受体促进tPA分泌，降低PAI-1浓度而增强纤溶系统活性，有利于防止血栓性疾病的发生。

Effects of testosterone on the fibrinolysis activity of HUVEC and its mechanism

AIM: To investigate the effect of testosterone with varied concentrations on the fibrinolysis activity of HUVEC and its mechanism.METHODS: Human umbilical vein endothelial cells (HUVEC) were cultured as recommended. After confluence, the cultures were treated with testosterone(3 ×10-10, 3×10-9, 3×10-8,3×10-6, 3×10-5 mol/L) , and the control confluent cells were cultured in the same medium without steroid. MTT experiment was repeated for 72 hours to investigate each groups’ cell proliferation. The tPA and PAI-1 antigen levels were assayed with ELISA Kits. Then with HUVEC incubated in androgen receptor antagonist (flutamide) 3 hours previously, the experiment was repeated. RESULTS: Testosterone at physiologic or lower concentrations (3 ×10-10 to 3×10-8 mol/L ) stimulated the secretion of tPA by HUVEC (P＜0.01). However, tPA levels markedly reduced at larger doses (3 ×10-6 to 3×10-5 mol/L). On the other hand， PAI-1 antigen levels decreased significantly at the testosterone concentrations ranging from 3 ×10-10 to 3×10-5 mol/L (P＜0.05). Flutamide attenuated the testosterone’s effects (P＜0.05). CONCLUSIONS: The results indicated that testosterone at physiologically relevant concentrations decreased PAI-1, while increased tPA levels via the androgen receptor, which suggested that testosterone may have beneficial effects on preventing thrombotic diseases.