雌激素对内皮细胞释放一氧化氮的作用

Effects of 17β-estradiol on the Release of Nitric Oxide from HUVEC

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10-9～10-5mol/LT、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和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的促进NO释放作用。10-4及10-3mol/LHcy刺激内皮细胞24h,NO释放减少,同时加入10-9～10-5mol/L17β-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。

Objective The protective mechanism of17β-estradiol on blood vessels was i nvestigated to pro vide evidences for clinical use of hormone replacement thera py in postmenopausal women.Methods To obs-erve the effects of17β-estradiol (17β-E 2 ),testosterone (T),homocysteine (Hcy),17β-E 2 combined with T and17β-E 2 combined with Hcy on the production of nitric oxide (NO)released from cult ured hu ma n umbilical endothelial cells (HUVEC)in vitro.Results Preincubatio n with10 -9 mol/L17β-E 2 8～48hours significantly enhanced the release of nitric oxide from HUVEC versus the con trol,but 10 -9 mol/L T had no effects within48hours.Pretreatment with10 -9 ～10 -7 mol/L testoste rone for24hours had no effects on the release of NO from HU VEC versus the control,but 10 -6 ,10 -5 mol/L T significantly red uced the release of NO from HUVEC.HUVEC were trea ted by10 -9 ～10 -5 mol/L17β-E 2 and10 -9 ～10 -5 mol/L T respectively for24hours.10 -9 ,10 -8 mol/L T had no effects on the beneficial effect of17β-E 2 with regard to the production of NO from HUVEC,while10 -5 mol/L T greatly attenuated the ben eficial effect of17β-E 2 with regard to the production of NO from HUVEC.Pretreatment with10 -4 ～10 -3 mol/L Hcy for24hours greatly inhibited the release of NO from HUVEC.If tr eated HUVEC with various concentrations of17β-E 2 (10 -9 ,10 -7 ,10 -5 mol/L)and Hcy for24hours simultaneously,10 -9 ～10 -7 mol/L17β-E 2 can partly eliminate the effects of Hcy on the released of NO from HUVEC.Co nclusions T can not enhance the release of NO from HUVECs.The effect of17β- E 2 combined with T on the release of NO depends on the concentration of both1 7β-E 2 and T.When17β-E 2 and T are in low dose,HUVEC can release more NO.Hcy can inhibit the release of NO from HUVEC,con comitant treatment with a low dose of17β-E 2 may eliminate the effects of Hcy on HUVEC.