Effect of dienogest on estrogen-induced nitric oxide production in human umbilical vein endothelial cells and endothelium-dependent vasodilatation in postmenopausal women
Effect of dienogest on estrogen-induced nitric oxide production in human umbilical vein endothelial cells and endothelium-dependent vasodilatation in postmenopausal women
复制标题
DOI：
10.1097/gme.0b013e3181d273c7
复制
发表时间：
2010-04
期刊：
影响因子：
--
通讯作者：
Noriko Henmi;Kazuhiro Takahashi;M. Amita;Keiko Takata;T. Ohta;S. Tsutsumi;Toshifumi Takahashi;
中科院分区：
文献类型：
--
作者：
Noriko Henmi;Kazuhiro Takahashi;M. Amita;Keiko Takata;T. Ohta;S. Tsutsumi;Toshifumi Takahashi;
目的：我们研究了地诺孕素（DNG）对雌激素在内皮功能中的有利作用的影响，地诺孕素（DNG）具有与天然孕酮（P4）相似的特征。研究方法：（1）分别用醋酸甲羟孕酮（MPA）、DNG、P_4和雌二醇（E_2）处理人脐静脉内皮细胞，检测内皮细胞一氧化氮（NO）的产生、Akt、ERK的磷酸化和内皮细胞NO合成酶的活性。(2)将20名手术绝经的妇女随机分为4组：对照组（未治疗）、E2单药组、E2 + MPA组和E2 + DNG组。治疗组于术后1周开始给予E2（0.72 mg/d）透皮治疗2 d，或E2 + MPA（2.5 mg/d）或E2 + DNG（2 mg/d）透皮治疗1周，对照组不使用激素。我们用超声检查了肱动脉血流介导的扩张（FMD）的变化。结果如下：（1）MPA抑制E2诱导的NO生成和Akt、细胞外信号调节激酶和内皮NO合成酶的磷酸化，但DNG和P4均不抑制E2的作用。(2)术后1周各组FMD均明显下降。E2可显著改善E2组内皮损伤（FMD，3.4% ± 0.9%~ 7.6% ± 1.3%）（P < 0.05），而E2 + MPA不能改善内皮损伤（3.3% ± 1.1%~ 3.5% ± 1.0%）。而E2 + DNG组FMD明显增加（2.9% ± 0.5%至8.7% ± 1.0%; P < 0.05）。结论：这些结果表明，DNG不抑制E2恢复血管舒张。DNG对接受激素治疗的绝经后妇女的内皮功能的影响可能优于MPA。
Objective: We investigated the effects of dienogest (DNG), which has a profile similar to that of natural progesterone (P4), on the favorable effects of estrogen in endothelial function. Methods: (1) Human umbilical vein endothelial cells were treated with medroxyprogesterone acetate (MPA), DNG, or P4 with or without estradiol (E2), and then we examined nitric oxide (NO) production, phosphorylation of Akt, ERK, and endothelial NO synthase. (2) Twenty women with surgical menopause were randomly allocated to four groups: control (no treatment), E2 alone, E2 + MPA, and E2 + DNG. The treatment groups were treated with transdermal E2 (0.72 mg) for 2 days or E2 + MPA (2.5 mg/d) or E2 + DNG (2 mg/d) for a week starting 1 week after the operation; the control group did not use hormone. We examined the changes in the flow-mediated dilatation (FMD) of the brachial artery using ultrasonography. Results: (1) Although MPA attenuated E2-induced NO production and phosphorylation of Akt, extracellular signal-regulated kinase, and endothelial NO synthase, neither DNG nor P4 inhibited E2 effects. (2) A significant decrease in FMD was observed 1 week after the operation in all groups. E2 significantly ameliorated endothelial impairment (FMD, 3.4% ± 0.9% to 7.6% ± 1.3%) in the E2-alone group (P < 0.05), but E2 + MPA could not ameliorate endothelial impairment (3.3% ± 1.1% to 3.5% ± 1.0%). However, FMD in the E2 + DNG group significantly increased (2.9% ± 0.5% to 8.7% ± 1.0%; P < 0.05). Conclusions: These results suggest that DNG did not inhibit the restoration of vasodilatation by E2. DNG may have an advantage compared with MPA on the endothelial function in postmenopausal women receiving hormone therapy.