Oparil S, Levine R L, Chen S J, Durand J, Chen Y F
University of Alabama at Birmingham, USA.
Circulation. 1997 Mar 4;95(5):1301-7. doi: 10.1161/01.cir.95.5.1301.
Estrogen blunts the neointimal response to vascular injury in gonadectomized rats of both sexes; addition of a progestin blocks the estrogen effect. This study tested, in intact rats of both sexes, whether (1) exogenous estrogen has a vasoprotective effect in injured carotid arteries, (2) progestin (medroxyprogesterone acetate, MPA) blocks the vasoprotective effect of estrogen, and (3) any observed sexual dimorphism in the responses to estrogen and/or MPA can be accounted for by differences in serum 17 beta-estradiol levels.
Intact male and female Sprague-Dawley rats were randomly divided into four subgroups treated with either (1) 17 beta-estradiol, (2) MPA, (3) 17 beta-estradiol + MPA, or (4) vehicle and were subjected to balloon injury of the right common carotid artery. Two weeks later, rats were killed by an overdose of pentobarbital, and the carotid arteries were evaluated for myointimal thickening. Neither estradiol nor MPA altered the neointimal response in males. In females, estradiol reduced and MPA enhanced the response, whereas addition of MPA to estradiol blocked the vasoprotective effects of estrogen.
Intact male rats but not intact females are resistant to the vasoprotective effects of exogenous estrogen, despite attainment of physiological (for females) serum 17 beta-estradiol levels. MPA enhances the neointimal response in intact females, presumably by blocking the production and thus the vasoprotective effect of endogenous estrogen.
雌激素可减弱两性去势大鼠血管损伤后的内膜增生反应；添加孕激素可阻断雌激素的作用。本研究在两性完整大鼠中检测：（1）外源性雌激素对损伤颈动脉是否具有血管保护作用；（2）孕激素（醋酸甲羟孕酮，MPA）是否阻断雌激素的血管保护作用；（3）观察到的雌激素和/或MPA反应中的性别差异是否可由血清17β-雌二醇水平差异来解释。
将雄性和雌性Sprague-Dawley大鼠随机分为四组，分别给予（1）17β-雌二醇、（2）MPA、（3）17β-雌二醇+MPA或（4）赋形剂，然后对右侧颈总动脉进行球囊损伤。两周后，过量戊巴比妥钠处死大鼠，评估颈动脉肌内膜增厚情况。雌二醇和MPA均未改变雄性大鼠的内膜增生反应。在雌性大鼠中，雌二醇减轻而MPA增强了内膜增生反应，而在雌二醇中添加MPA则阻断了雌激素的血管保护作用。
尽管达到了生理水平（对雌性而言）的血清17β-雌二醇水平，但完整雄性大鼠而非完整雌性大鼠对外源性雌激素的血管保护作用具有抗性。MPA增强了完整雌性大鼠的内膜增生反应，推测是通过阻断内源性雌激素的产生从而阻断其血管保护作用。
