雌激素对内皮细胞释放一氧化氮的作用

目的：探讨雌激素对血管保护作用的机制,为绝经后妇女应用激素替代治疗提供参考。方法：观察10^-9～10^-5mol/L17β－雌二醇（17β－E2）、睾酮（T）、10^-4及10^-3mol/L同型半胱氨酸（Hcy)单独应用和10^-9～10^-5mol/L17β-E2分别与1010^-9～10^-5mol/L T、10^-9～10^-5mol/L17β－E2分别与10^-4及10^-3mol/LHcy联合应用对原代培养脐静脉内皮细胞释放一氧化氮（NO）的影响。结果：10^-9mol/L17β－E2刺激内皮细胞8－48h,NO释放明显增多;10^-9mol/LT刺激内皮细胞2－48h,NO无明显增多。10^-9～10^-7mol/LT刺激内皮细胞24h,培养液中NO水平无明显改变,10^-6及10^-5mol/LT使培养液中的NO明显减少。当10^-9～10^-5mol/LE2与10^-9～10^-5mol/LT分别联合应用刺激内皮细胞时,10^-9～10^-8mol/LT不影响17β-E2的促进NO释放作用,而10^-7～10^-5mol/LT抑制17β－E2,10^-9～10^-7mol/L17β－E2能改善Hcy对内皮细胞的损伤作用,10^-5mol/L17β－E2则无此作用。结论：T不能促进人脐静脉内皮细胞释放NO。T具有抑制17β－E2促进内皮细胞释放NO的作用,尤其在17β-E2、T浓度较高时作用更明显。高浓度Hcy对内皮细胞释放NO产生抑制作用,但加入17β-E2可减轻Hcy的抑制作用。

Effects of 17 beta-estradiol on the release of nitric oxide from HUVEC

OBJECTIVE: The protective mechanism of 17 beta-estradiol on blood vessels was investigated to provide evidences for clinical use of hormone replacement therapy in postmenopausal women. METHODS: To observe the effects of 17 beta-estradiol (17 beta-E2), testosterone (T), homocysteine (Hcy), 17 beta-E2 combined with T and 17 beta-E2 combined with Hcy on the production of nitric oxide (NO) released from cultured human umbilical endothelial cells (HUVEC) in vitro. RESULTS: Preincubation with 10(-9) mol/L 17 beta-E2 8-48 hours significantly enhanced the release of nitric oxide from HUVEC versus the control, but 10(-9) mol/L T had no effects within 48 hours. Pretreatment with 10(-9)-10(-7) mol/L testosterone for 24 hours had no effects on the release of NO from HUVEC versus the control, but 10(-6), 10(-5) mol/L T significantly reduced the release of NO from HUVEC. HUVEC were treated by 10(-9)-10(-5) mol/L 17 beta-E2 and 10(-9)-10(-5) mol/L T respectively for 24 hours. 10(-9), 10(-8) mol/L T had no effects on the beneficial effect of 17 beta-E2 with regard to the production of NO from HUVEC, while 10(-5) mol/L T greatly attenuated the beneficial effect of 17 beta-E2 with regard to the production of NO from HUVEC. Pretreatment with 10(-4)-10(-3) mol/L Hcy for 24 hours greatly inhibited the release of NO from HUVEC. If treated HUVEC with various concentrations of 17 beta-E2 (10(-9), 10(-7), 10(-5) mol/L) and Hcy for 24 hours simultaneously, 10(-9)-10(-7) mol/L 17 beta-E2 can partly eliminate the effects of Hcy on the released of NO from HUVEC. CONCLUSIONS: T can not enhance the release of NO from HUVECs. The effect of 17 beta-E2 combined with T on the release of NO depends on the concentration of both 17 beta-E2 and T. When 17 beta-E2 and T are in low dose, HUVEC can release more NO. Hcy can inhibit the release of NO from HUVEC, concomitant treatment with a low dose of 17 beta-E2 may eliminate the effects of Hcy on HUVEC.