Li ShiJun, Li XiaoYing, Li Jian, Deng Xinli, Li Yan
Division of Geriatric Cardiology, Chinese PLA General Hospital at No. 28, Fuxing Road, Beijing 100853, PR China.
Steroids. 2007 Nov;72(13):875-80. doi: 10.1016/j.steroids.2007.07.007. Epub 2007 Jul 24.
Platelets play a crucial role in the development of arterial thrombosis and other pathophysiologies leading to clinical ischemic events. Defective regulation of platelet activation/aggregation is a predominant cause for arterial thrombosis. The purposes of our study are to assess the effect of androgen at physiological concentration via its receptor on oxidative-stress-induced platelet aggregation and to further elucidate the possible mechanism.
Plasma dihydrotestosterone (DHT) was determined by ELISA using a commercially available kit. Platelet aggregometer was used to measure platelet aggregation. The contents of thromboxane B(2) (TXB(2)) were assayed with radio-immunoassay. Our results showed that addition of DHT (2 nM) significantly inhibited platelet aggregation induced by hydrogen peroxide (H(2)O(2)) (10 mM, 25 mM) in PRP diluted with Tyrode's buffer. Moreover, H(2)O(2)-induced platelet aggregation decreased in sham-operated rats. However, H(2)O(2)-induced platelet aggregation significantly increased in castrated rats. Replacement of DHT inhibited H(2)O(2)-induced platelet aggregation in castrated rats. After PRP was pretreated with flutamide, H(2)O(2)-induced platelet aggregation increased in castrated rats again. Presence of DHT (2 nM) obviously inhibited H(2)O(2)-induced thromboxane A(2) (TXA(2)) release in castrated rats. Pretreatment of DHT and flutamide increased H(2)O(2)-stimulated TXA(2) release from platelet in castrated rats again. Castration caused a significant reduction in plasma testosterone and DHT levels, whereas DHT replaced at a dose of 0.25 mg/rat restored the circulating DHT to physiological levels, without being altered by treatment with flutamide. The plasma TXB(2) increased in castrated rats as compared with that in sham-operated rats. Replacement with DHT reduced plasma TXB(2) contents in castrated rats. However, flutamide supplementation increased plasma contents of TXB(2) in castrated rats again.
Androgen at physiological doses via its receptor inhibits oxidative-stress-induced platelet aggregation, which is associated with the reduction of TXA(2) release from platelets.
血小板在动脉血栓形成及导致临床缺血事件的其他病理生理过程中起关键作用。血小板激活/聚集调节缺陷是动脉血栓形成的主要原因。本研究的目的是评估生理浓度的雄激素通过其受体对氧化应激诱导的血小板聚集的影响，并进一步阐明其可能机制。
采用市售试剂盒通过酶联免疫吸附测定法（ELISA）测定血浆双氢睾酮（DHT）。使用血小板聚集仪测量血小板聚集。用放射免疫分析法检测血栓素B₂（TXB₂）的含量。我们的结果显示，在用台氏缓冲液稀释的富血小板血浆（PRP）中加入DHT（2 nM）可显著抑制过氧化氢（H₂O₂）（10 mM、25 mM）诱导的血小板聚集。此外，假手术大鼠中H₂O₂诱导的血小板聚集减少。然而，去势大鼠中H₂O₂诱导的血小板聚集显著增加。补充DHT可抑制去势大鼠中H₂O₂诱导的血小板聚集。用氟他胺预处理PRP后，去势大鼠中H₂O₂诱导的血小板聚集再次增加。DHT（2 nM）的存在明显抑制去势大鼠中H₂O₂诱导的血栓素A₂（TXA₂）释放。DHT和氟他胺预处理再次增加了去势大鼠中H₂O₂刺激的血小板TXA₂释放。去势导致血浆睾酮和DHT水平显著降低，而以0.25 mg/大鼠的剂量补充DHT可使循环中的DHT恢复到生理水平，且不受氟他胺治疗的影响。与假手术大鼠相比，去势大鼠血浆TXB₂增加。补充DHT可降低去势大鼠血浆TXB₂含量。然而，补充氟他胺再次增加了去势大鼠血浆TXB₂含量。
生理剂量的雄激素通过其受体抑制氧化应激诱导的血小板聚集，这与血小板TXA₂释放减少有关。
